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class="uploads-container" id="social-redesign-work-container"><div class="upload-header"><h2 class="ds2-5-heading-sans-serif-xs">Uploads</h2></div><div class="documents-container backbone-social-profile-documents" style="width: 100%;"><div class="u-taCenter"></div><div class="profile--tab_content_container js-tab-pane tab-pane active" id="all"><div class="profile--tab_heading_container js-section-heading" data-section="Papers" id="Papers"><h3 class="profile--tab_heading_container">Papers by Fred Opperdoes</h3></div><div class="js-work-strip profile--work_container" data-work-id="121259594"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/121259594/The_Glycosome_of_Trypanosomatids"><img alt="Research paper thumbnail of The Glycosome of Trypanosomatids" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/121259594/The_Glycosome_of_Trypanosomatids">The Glycosome of Trypanosomatids</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 2010</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of perox...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of peroxisomes present in almost all eukaryotic cells. Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="121259594"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="121259594"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 121259594; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=121259594]").text(description); $(".js-view-count[data-work-id=121259594]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 121259594; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='121259594']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 121259594, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=121259594]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":121259594,"title":"The Glycosome of Trypanosomatids","translated_title":"","metadata":{"abstract":"ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. 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Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.","internal_url":"https://www.academia.edu/121259594/The_Glycosome_of_Trypanosomatids","translated_internal_url":"","created_at":"2024-06-19T22:52:58.113-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_Glycosome_of_Trypanosomatids","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of peroxisomes present in almost all eukaryotic cells. Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":231661,"name":"Enzyme","url":"https://www.academia.edu/Documents/in/Enzyme"},{"id":433495,"name":"Biosynthesis","url":"https://www.academia.edu/Documents/in/Biosynthesis"},{"id":534463,"name":"Peroxisome","url":"https://www.academia.edu/Documents/in/Peroxisome"},{"id":764799,"name":"Metabolic pathway","url":"https://www.academia.edu/Documents/in/Metabolic_pathway"},{"id":3647879,"name":"Springer Ebooks","url":"https://www.academia.edu/Documents/in/Springer_Ebooks"}],"urls":[{"id":43085294,"url":"https://doi.org/10.1007/978-3-642-12863-9_12"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="121259580"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/121259580/Abstracts_of_papers_medicinal_chemistry_meeting"><img alt="Research paper thumbnail of Abstracts of papers medicinal chemistry meeting" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/121259580/Abstracts_of_papers_medicinal_chemistry_meeting">Abstracts of papers medicinal chemistry meeting</a></div><div class="wp-workCard_item"><span>Pharmaceutisch Weekblad Scientific Edition</span><span>, 1988</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR&#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR&#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR&#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR&#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR&#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR&#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, &quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F&amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="121259580"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="121259580"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 121259580; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=121259580]").text(description); $(".js-view-count[data-work-id=121259580]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 121259580; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='121259580']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 121259580, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=121259580]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":121259580,"title":"Abstracts of papers medicinal chemistry meeting","translated_title":"","metadata":{"abstract":"s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR\u0026#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR\u0026#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR\u0026#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR\u0026#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR\u0026#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR\u0026#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, \u0026quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F\u0026amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…","publisher":"Springer Science and Business Media LLC","publication_date":{"day":null,"month":null,"year":1988,"errors":{}},"publication_name":"Pharmaceutisch Weekblad Scientific Edition"},"translated_abstract":"s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR\u0026#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR\u0026#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR\u0026#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR\u0026#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR\u0026#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR\u0026#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, \u0026quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F\u0026amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…","internal_url":"https://www.academia.edu/121259580/Abstracts_of_papers_medicinal_chemistry_meeting","translated_internal_url":"","created_at":"2024-06-19T22:52:33.819-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Abstracts_of_papers_medicinal_chemistry_meeting","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR\u0026#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR\u0026#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR\u0026#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR\u0026#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR\u0026#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR\u0026#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, \u0026quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F\u0026amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":41839,"name":"Clinical Chemistry","url":"https://www.academia.edu/Documents/in/Clinical_Chemistry"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="116147126"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/116147126/Glycosome_Biogenesis_in_Trypanosoma_Brucei"><img alt="Research paper thumbnail of Glycosome Biogenesis in Trypanosoma Brucei" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/116147126/Glycosome_Biogenesis_in_Trypanosoma_Brucei">Glycosome Biogenesis in Trypanosoma Brucei</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="116147126"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="116147126"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 116147126; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809714"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809714/Using_Metabolic_Control_Analysis_To_Improve_The_Selectivity_and_Effectiveness_of_Drugs_Against_Parasitic_Diseases"><img alt="Research paper thumbnail of Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809714/Using_Metabolic_Control_Analysis_To_Improve_The_Selectivity_and_Effectiveness_of_Drugs_Against_Parasitic_Diseases">Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Trypanosoma brucei is the parasite that causes African sleeping sickness in humans and the relate...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Trypanosoma brucei is the parasite that causes African sleeping sickness in humans and the related disease nagana in cattle. The development of drugs is hampered by the many similarities between this parasite and the cells of its host. Until now advanced drug-design strategies have focussed on the differences between the three-dimensional structure of trypanosome and human enzymes (Verlinde &amp;amp;amp;amp;amp; Hol,</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809714"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809714"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809714; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809714]").text(description); $(".js-view-count[data-work-id=113809714]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809714; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809714']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809714, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809714]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809714,"title":"Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases","translated_title":"","metadata":{"abstract":"Trypanosoma brucei is the parasite that causes African sleeping sickness in humans and the related disease nagana in cattle. 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It discusses the carbohydrate metabolism of the malaria parasite Plasmodium and highlights that nothing is known about the carbohydrate metabolism of the stages of the life cycle other than the one that infects the red blood cell. Even for this stage information on glycolysis and mitochondrial metabolism is highly fragmented. Energy generation occurs predominantly through fermentation of glucose with the production of lactate as the major end-product. The Trypanosomatidae are characterized by a high flexibility of their energy metabolism. They contain a single mitochondrion at all developmental stages of which the contribution to the overall adenosine triphosphate generation varies significantly from one member of the trypanosomatid family to another and from one life-cycle stage to another. In all the Trypanosomatidae studied, glycolysis takes place via the Embden-Meyerhoff pathway of which the early enzymes are sequestered inside a sub-cellular organelle: the glycosome. Little is known about the role and properties of the individual enzymes involved in carbohydrate metabolism, mainly because of difficulties in obtaining sufficient parasite material free of host cell contamination. Rapid progress is now being made through the molecular cloning of several glycolytic enzymes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809713"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809713"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809713; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809713]").text(description); $(".js-view-count[data-work-id=113809713]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809713; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809713']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809713, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809713]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809713,"title":"Carbohydrate and Energy Metabolism in Aerobic Protozoa","translated_title":"","metadata":{"abstract":"Publisher Summary This chapter discusses the African trypanosome: Trypanosoma brucei, and other species of the Trypanosoma, and Leishmania genera. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809711"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809711/Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases"><img alt="Research paper thumbnail of Toward The Development Of New Drugs For Parasitic Diseases" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809711/Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases">Toward The Development Of New Drugs For Parasitic Diseases</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 1983</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809711"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809711"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809711; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809711]").text(description); $(".js-view-count[data-work-id=113809711]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809711; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809711']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809711, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809711]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809711,"title":"Toward The Development Of New Drugs For Parasitic Diseases","translated_title":"","metadata":{"abstract":"The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.","publisher":"Springer Nature","publication_date":{"day":null,"month":null,"year":1983,"errors":{}},"publication_name":"Springer eBooks"},"translated_abstract":"The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.","internal_url":"https://www.academia.edu/113809711/Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases","translated_internal_url":"","created_at":"2024-01-21T02:18:44.702-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":164,"name":"Parasitology","url":"https://www.academia.edu/Documents/in/Parasitology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":3647879,"name":"Springer Ebooks","url":"https://www.academia.edu/Documents/in/Springer_Ebooks"}],"urls":[{"id":38775288,"url":"https://doi.org/10.1007/978-1-4612-5550-5_16"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809710"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809710/Aerobic_Protists_Trypanosomatidae"><img alt="Research paper thumbnail of Aerobic Protists—Trypanosomatidae" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809710/Aerobic_Protists_Trypanosomatidae">Aerobic Protists—Trypanosomatidae</a></div><div class="wp-workCard_item"><span>Elsevier eBooks</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, pr...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809710"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809710"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809710; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809710]").text(description); $(".js-view-count[data-work-id=113809710]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809710; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809710']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809710, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809710]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809710,"title":"Aerobic Protists—Trypanosomatidae","translated_title":"","metadata":{"abstract":"Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.","publisher":"Elsevier BV","publication_date":{"day":null,"month":null,"year":2003,"errors":{}},"publication_name":"Elsevier eBooks"},"translated_abstract":"Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.","internal_url":"https://www.academia.edu/113809710/Aerobic_Protists_Trypanosomatidae","translated_internal_url":"","created_at":"2024-01-21T02:18:44.541-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Aerobic_Protists_Trypanosomatidae","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":375896,"name":"Trypanosoma","url":"https://www.academia.edu/Documents/in/Trypanosoma"},{"id":3983118,"name":"Molecular medical parasitology","url":"https://www.academia.edu/Documents/in/Molecular_medical_parasitology"}],"urls":[{"id":38775287,"url":"https://doi.org/10.1016/b978-012473346-6/50009-0"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809709"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809709/Biogenesis_and_Evolutionary_Origin_of_Peroxisomes"><img alt="Research paper thumbnail of Biogenesis and Evolutionary Origin of Peroxisomes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809709/Biogenesis_and_Evolutionary_Origin_of_Peroxisomes">Biogenesis and Evolutionary Origin of Peroxisomes</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 1989</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most euka...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. They may have quite different functions within the eukaryotic cell (Lazarow and Fujiki, 1985; Huang et al, 1983; Opperdoes, 1987). Table 1 gives an overview of the principal metabolic pathways that have been found in microbodies. Despite such differences in function, it is now generally accepted that all these microbodies are members of one family of organelles. Morphologically, they have the same appearance. They are round or oval-shaped, but range in size from 0.2 to 1 micrometer. They are surrounded by a single membrane and have an electron-dense matrix, which sometimes contains a crystalloid inclusion (Fig. 1). They are found in almost all eukaryotic cells, such as protozoa, fungi, plants and animals. All microbodies have beta-oxidation as the common pathway. Peroxide metabolism, consisting of H202-producing oxidases and catalase, was originally thought to be the main characteristic of these organelles, since catalase is present in the microbodies of most organisms. However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809709"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809709"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809709; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809709]").text(description); $(".js-view-count[data-work-id=113809709]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809709; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809709']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809709, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809709]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809709,"title":"Biogenesis and Evolutionary Origin of Peroxisomes","translated_title":"","metadata":{"abstract":"In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. They may have quite different functions within the eukaryotic cell (Lazarow and Fujiki, 1985; Huang et al, 1983; Opperdoes, 1987). Table 1 gives an overview of the principal metabolic pathways that have been found in microbodies. Despite such differences in function, it is now generally accepted that all these microbodies are members of one family of organelles. Morphologically, they have the same appearance. They are round or oval-shaped, but range in size from 0.2 to 1 micrometer. They are surrounded by a single membrane and have an electron-dense matrix, which sometimes contains a crystalloid inclusion (Fig. 1). They are found in almost all eukaryotic cells, such as protozoa, fungi, plants and animals. All microbodies have beta-oxidation as the common pathway. Peroxide metabolism, consisting of H202-producing oxidases and catalase, was originally thought to be the main characteristic of these organelles, since catalase is present in the microbodies of most organisms. However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.","publisher":"Springer Nature","publication_date":{"day":null,"month":null,"year":1989,"errors":{}},"publication_name":"Springer eBooks"},"translated_abstract":"In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. They may have quite different functions within the eukaryotic cell (Lazarow and Fujiki, 1985; Huang et al, 1983; Opperdoes, 1987). Table 1 gives an overview of the principal metabolic pathways that have been found in microbodies. Despite such differences in function, it is now generally accepted that all these microbodies are members of one family of organelles. Morphologically, they have the same appearance. They are round or oval-shaped, but range in size from 0.2 to 1 micrometer. They are surrounded by a single membrane and have an electron-dense matrix, which sometimes contains a crystalloid inclusion (Fig. 1). They are found in almost all eukaryotic cells, such as protozoa, fungi, plants and animals. All microbodies have beta-oxidation as the common pathway. Peroxide metabolism, consisting of H202-producing oxidases and catalase, was originally thought to be the main characteristic of these organelles, since catalase is present in the microbodies of most organisms. However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.","internal_url":"https://www.academia.edu/113809709/Biogenesis_and_Evolutionary_Origin_of_Peroxisomes","translated_internal_url":"","created_at":"2024-01-21T02:18:44.355-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Biogenesis_and_Evolutionary_Origin_of_Peroxisomes","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. 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However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":161099,"name":"Biogenesis","url":"https://www.academia.edu/Documents/in/Biogenesis"},{"id":534463,"name":"Peroxisome","url":"https://www.academia.edu/Documents/in/Peroxisome"},{"id":3647879,"name":"Springer Ebooks","url":"https://www.academia.edu/Documents/in/Springer_Ebooks"}],"urls":[{"id":38775286,"url":"https://doi.org/10.1007/978-1-4613-0545-3_13"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809707"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809707/Phylogenetic_analysis_using_protein_sequences"><img alt="Research paper thumbnail of Phylogenetic analysis using protein sequences" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809707/Phylogenetic_analysis_using_protein_sequences">Phylogenetic analysis using protein sequences</a></div><div class="wp-workCard_item"><span>Cambridge University Press eBooks</span><span>, Jun 17, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809707"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809707"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809707; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809706"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/113809706/Biogenesis_of_the_glycosome_in_Trypanosoma_brucei_the_synthesis_translocation_and_turnover_of_glycosomal_polypeptides"><img alt="Research paper thumbnail of Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides" class="work-thumbnail" src="https://attachments.academia-assets.com/110676170/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/113809706/Biogenesis_of_the_glycosome_in_Trypanosoma_brucei_the_synthesis_translocation_and_turnover_of_glycosomal_polypeptides">Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides</a></div><div class="wp-workCard_item"><span>The EMBO Journal</span><span>, May 1, 1987</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Communicated by C.de Duve Glycosomes, the microbodies of Trypanosoma brucei, contain a number of ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Communicated by C.de Duve Glycosomes, the microbodies of Trypanosoma brucei, contain a number of enzymes involved in glucose and glycerol metabolism. The biogenesis of three of these enzymes has been studied. Aldolase, D-glyceraldehyde-3-phosphate dehydrogenase and NAD-linked glycerol-3-phosphate dehydrogenase are all synthesized in the cytosol on free rather than on membrane-bound polysomes. In vitro, as well as in vivo, these polypeptides are synthesized at their mature size, and no evidence was found for any processing upon entry into the glycosomes. Continuous and pulse-chase labelling experiments with procyclic trypomastigotes revealed that the enzymes have a half-life in the cytosol of-3 min or less, and then turn over rapidly in the glycosomes, with half-lives as short as 30 min.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="9e8e28c2c0c42eb9c754ae3db3708cc3" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":110676170,"asset_id":113809706,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/110676170/download_file?st=MTczNjkzMjc1NSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809706"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809706"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809706; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809706]").text(description); $(".js-view-count[data-work-id=113809706]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809706; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809706']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809706, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "9e8e28c2c0c42eb9c754ae3db3708cc3" } } $('.js-work-strip[data-work-id=113809706]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809706,"title":"Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides","translated_title":"","metadata":{"publisher":"Nature Portfolio","grobid_abstract":"Communicated by C.de Duve Glycosomes, the microbodies of Trypanosoma brucei, contain a number of enzymes involved in glucose and glycerol metabolism. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="107724686"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/107724686/The_Glycosome_of_Leishmania_as_a_Possible_Target_for_Chemotherapeutic_Attack"><img alt="Research paper thumbnail of The Glycosome of Leishmania as a Possible Target for Chemotherapeutic Attack" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/107724686/The_Glycosome_of_Leishmania_as_a_Possible_Target_for_Chemotherapeutic_Attack">The Glycosome of Leishmania as a Possible Target for Chemotherapeutic Attack</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 1989</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Basic studies over the last ten years have revealed that all Try-panosomatidae harbour a number o...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Basic studies over the last ten years have revealed that all Try-panosomatidae harbour a number of biochemical features unique in Nature. 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They belong to the family of perox...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of peroxisomes present in almost all eukaryotic cells. Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="121259594"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="121259594"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 121259594; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=121259594]").text(description); $(".js-view-count[data-work-id=121259594]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 121259594; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='121259594']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 121259594, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=121259594]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":121259594,"title":"The Glycosome of Trypanosomatids","translated_title":"","metadata":{"abstract":"ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of peroxisomes present in almost all eukaryotic cells. Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.","publisher":"Springer Nature","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Springer eBooks"},"translated_abstract":"ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of peroxisomes present in almost all eukaryotic cells. Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.","internal_url":"https://www.academia.edu/121259594/The_Glycosome_of_Trypanosomatids","translated_internal_url":"","created_at":"2024-06-19T22:52:58.113-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"The_Glycosome_of_Trypanosomatids","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"ABSTRACT Glycosomes are the microbodies of the Kinetoplastida. They belong to the family of peroxisomes present in almost all eukaryotic cells. Glycosomes share the same machinery for their biosynthesis and several metabolic pathways with the microbodies of other organisms. However, glycosomes contain in addition the enzymes of glycolysis and glycerol metabolism, gluconeogenesis, purine salvage, and pyrimidine biosynthesis, traits normally not encountered in other microbodies. The unique aspects of the trypanosomatid glycosome render this organelle and its constituents interesting targets for the development of new antitrypanosome drugs.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":145,"name":"Biochemistry","url":"https://www.academia.edu/Documents/in/Biochemistry"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":231661,"name":"Enzyme","url":"https://www.academia.edu/Documents/in/Enzyme"},{"id":433495,"name":"Biosynthesis","url":"https://www.academia.edu/Documents/in/Biosynthesis"},{"id":534463,"name":"Peroxisome","url":"https://www.academia.edu/Documents/in/Peroxisome"},{"id":764799,"name":"Metabolic pathway","url":"https://www.academia.edu/Documents/in/Metabolic_pathway"},{"id":3647879,"name":"Springer Ebooks","url":"https://www.academia.edu/Documents/in/Springer_Ebooks"}],"urls":[{"id":43085294,"url":"https://doi.org/10.1007/978-3-642-12863-9_12"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="121259580"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/121259580/Abstracts_of_papers_medicinal_chemistry_meeting"><img alt="Research paper thumbnail of Abstracts of papers medicinal chemistry meeting" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/121259580/Abstracts_of_papers_medicinal_chemistry_meeting">Abstracts of papers medicinal chemistry meeting</a></div><div class="wp-workCard_item"><span>Pharmaceutisch Weekblad Scientific Edition</span><span>, 1988</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR&#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR&#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR&#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR&#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR&#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR&#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, &quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F&amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="121259580"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="121259580"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 121259580; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=121259580]").text(description); $(".js-view-count[data-work-id=121259580]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 121259580; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='121259580']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 121259580, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=121259580]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":121259580,"title":"Abstracts of papers medicinal chemistry meeting","translated_title":"","metadata":{"abstract":"s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR\u0026#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR\u0026#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR\u0026#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR\u0026#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR\u0026#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR\u0026#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, \u0026quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F\u0026amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…","publisher":"Springer Science and Business Media LLC","publication_date":{"day":null,"month":null,"year":1988,"errors":{}},"publication_name":"Pharmaceutisch Weekblad Scientific Edition"},"translated_abstract":"s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR\u0026#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR\u0026#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR\u0026#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR\u0026#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR\u0026#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR\u0026#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, \u0026quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F\u0026amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…","internal_url":"https://www.academia.edu/121259580/Abstracts_of_papers_medicinal_chemistry_meeting","translated_internal_url":"","created_at":"2024-06-19T22:52:33.819-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Abstracts_of_papers_medicinal_chemistry_meeting","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"s of papers PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR G. Lambrecht and E. Mutschler Acetylcholine (ACh) receptors are classified pharmacologically into two major categories, denoted as nicotinic and muscarinic cholinergic receptors (MAChR). MAChR\u0026#39;s are glycosylated membrane-spanning proteins. Thefr stimulation leads to a wide variety of physiological responses (both excitatory and inhibitory) in both the central and peripheral nervous system. These di f ferent cellular responses are the consequence of the abil i ty of MAChR\u0026#39;s to activate different effector mechanisms. These include: ( i) inhibition of adenylate cyclase; ( i i ) opening and closing of ion channels and ( i i i ) stimulation of phosphatidylinositol metabolism. GTP-binding proteins are involved in these receptor effector coupling mechanisms. In addition to effector tissues such as heart, smooth muscle and various glands, MAChR\u0026#39;s are located on peripheral and central neurones. These receptors exist not only on the postsynaptic membrane, but on presynaptic elements as well. The prejunctional MAChR\u0026#39;s (autoreceptors/heteroreceptors) participate in the regulation of neurotransmitter release. There are at least four pharmacological subtypes of the MAChR\u0026#39;s (Mla , MIB, M2a, M2B) which can be discriminated by selective drugs (e.g. pirenzepine, methoctramine, hexahydro-sila-difenidol). Cloning studies have revealed that the MAChR subtypes are different gene products and have different primary sequences. MAChR\u0026#39;s are dynamic structures, responsive to various changes in the receptor environment. Thus, physiologically relevant fluctuations in receptor af f in i ty and concentrations can have important clinical implications in the pathophysiology of various disorders, such as Alzheimers and related diseases, in which a cholinergic deficit has been reported. Department of Pharmacology, University of Frankfurt, Theodor-Stern-Kai 7, D-6000 Frankfurt/M., FRG. I~JSCARINIC RE~a-~u,lS: TOPOGRAPHY AND SECOND MESS~%~4~RS J.A.D.M. Tonnaer, \u0026quot;In. de Boer and A.M.L. van Delft Cholinergic signal transduction is mediated by two types of acetylcholine receptors, classified as nicotinic and muscarinic. StinJlation of the nicotinic receptor results in the opening of a transmlmbrane channel, whilst muscarlnlc e f f e c t s are thought to be mediated by second messengers (cAMP, cGMP, IP3 and DG). With the advance of the discriminating antagonists pirenzeplne (FZ), AF-DX 116 and 4~, a complex heterogeneity of muscarinic receptors has been described. FZ-sensitlve 141 receptors in the brain predominate in rostral structures such as cortex, striat~m and hil~x)camix~, whilst F\u0026amp;-insensitive M2A and M2B receptors appear more even].y distributed over the brain. Muscarinic M2 receptors in the striatum are negatively coupled to adenylate cyclase and inhibit the formation of cAMP. cGMP formatio~ and ~hosphoinositide turnover are triggered by mumcarlnie receptor stimulation in various brain structures. Available evidence suggests the involvement of an 142 receptor in hippocampal production~ whilst M1 and M2 receptors appear coupled to the phosph6inosltide cycle In the cortex and strlatum, respectively. In addition, regional differences in receptor-effector coupling may explain different second messenger responses to receptor stimulation in distinct brain structures. Differential efficacy of receptor-effector coupling is a complicating factor in the design of receptor subtypespecific agonists. Thus, presently available M1 preferring ~n rtial agonists ( cf. McN-A343 ) lack potency on efficiently coupled MI receptor systems, whilst M2-preferrlng but full agonists are highly active. It is likely that selective receptor affinity is not necessarily related to partial or full agonistic properties. Ml-preferring agnnists with the capacity to stimulate ~tl receptors may w~ll be designed in the near future t he re fo re . CqS Pharmacology Dept. , S c i e n t i f i c Development Group, Organon I n t e r n a t i o n a l , P.O. Box 20, 5340 mq Oss, The Netherlands. V o l . Io I 9 8 8 Pharmaceutisch Weekblad Scien.fic Edition 9 7 SELECTIVE MUSCARINIC ANTAGONISTS AS TOOLS FOR RECEPTORSUBCLASS IFI CAT ION G. M/hm The heterogeneity of muscarlnic receptors (mAChr) Is now w e l l es tab l ished. Strong impetus f o r a t e n t a t i v e subclassification came from the antiuleer-drug Plrenzeplne (PZ). High sfflntly FZ-blndlngs sites are termed H 1receptors, low a f f i n i t y binding s i t es M2-recep~ors. Heanwhtle, PZ-analogs have been found w i th a s i m i l a r M 1s e l e c t i v i t y profile. Structural features contributing t o their activity and receptor selectivity wlll be presented. Fur ther support f o r the concept of M1/M2-subclaasi f tcat ion was p r o v i d e d by the d i s c o v e r y o f AF-DX 116, a FZ-ana log which d i s p l a y s h l g h a f f i n i t y to c a r d i a c m u s c a r l n l e r e c e p t o r s . Moreover , h i n t s f o r M2recep to r h e t e r…","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":41839,"name":"Clinical Chemistry","url":"https://www.academia.edu/Documents/in/Clinical_Chemistry"},{"id":3789884,"name":"Pharmacology and pharmaceutical sciences","url":"https://www.academia.edu/Documents/in/Pharmacology_and_pharmaceutical_sciences"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="116147126"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/116147126/Glycosome_Biogenesis_in_Trypanosoma_Brucei"><img alt="Research paper thumbnail of Glycosome Biogenesis in Trypanosoma Brucei" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/116147126/Glycosome_Biogenesis_in_Trypanosoma_Brucei">Glycosome Biogenesis in Trypanosoma Brucei</a></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="116147126"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="116147126"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 116147126; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809714"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809714/Using_Metabolic_Control_Analysis_To_Improve_The_Selectivity_and_Effectiveness_of_Drugs_Against_Parasitic_Diseases"><img alt="Research paper thumbnail of Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809714/Using_Metabolic_Control_Analysis_To_Improve_The_Selectivity_and_Effectiveness_of_Drugs_Against_Parasitic_Diseases">Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 2000</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Trypanosoma brucei is the parasite that causes African sleeping sickness in humans and the relate...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Trypanosoma brucei is the parasite that causes African sleeping sickness in humans and the related disease nagana in cattle. The development of drugs is hampered by the many similarities between this parasite and the cells of its host. Until now advanced drug-design strategies have focussed on the differences between the three-dimensional structure of trypanosome and human enzymes (Verlinde &amp;amp;amp;amp;amp; Hol,</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809714"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809714"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809714; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809714]").text(description); $(".js-view-count[data-work-id=113809714]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809714; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809714']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809714, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809714]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809714,"title":"Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases","translated_title":"","metadata":{"abstract":"Trypanosoma brucei is the parasite that causes African sleeping sickness in humans and the related disease nagana in cattle. 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It discusses the carbohydrate metabolism of the malaria parasite Plasmodium and highlights that nothing is known about the carbohydrate metabolism of the stages of the life cycle other than the one that infects the red blood cell. Even for this stage information on glycolysis and mitochondrial metabolism is highly fragmented. Energy generation occurs predominantly through fermentation of glucose with the production of lactate as the major end-product. The Trypanosomatidae are characterized by a high flexibility of their energy metabolism. They contain a single mitochondrion at all developmental stages of which the contribution to the overall adenosine triphosphate generation varies significantly from one member of the trypanosomatid family to another and from one life-cycle stage to another. In all the Trypanosomatidae studied, glycolysis takes place via the Embden-Meyerhoff pathway of which the early enzymes are sequestered inside a sub-cellular organelle: the glycosome. Little is known about the role and properties of the individual enzymes involved in carbohydrate metabolism, mainly because of difficulties in obtaining sufficient parasite material free of host cell contamination. Rapid progress is now being made through the molecular cloning of several glycolytic enzymes.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809713"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809713"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809713; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809713]").text(description); $(".js-view-count[data-work-id=113809713]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809713; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809713']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809713, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809713]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809713,"title":"Carbohydrate and Energy Metabolism in Aerobic Protozoa","translated_title":"","metadata":{"abstract":"Publisher Summary This chapter discusses the African trypanosome: Trypanosoma brucei, and other species of the Trypanosoma, and Leishmania genera. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809711"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809711/Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases"><img alt="Research paper thumbnail of Toward The Development Of New Drugs For Parasitic Diseases" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809711/Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases">Toward The Development Of New Drugs For Parasitic Diseases</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 1983</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809711"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809711"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809711; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809711]").text(description); $(".js-view-count[data-work-id=113809711]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809711; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809711']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809711, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809711]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809711,"title":"Toward The Development Of New Drugs For Parasitic Diseases","translated_title":"","metadata":{"abstract":"The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.","publisher":"Springer Nature","publication_date":{"day":null,"month":null,"year":1983,"errors":{}},"publication_name":"Springer eBooks"},"translated_abstract":"The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.","internal_url":"https://www.academia.edu/113809711/Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases","translated_internal_url":"","created_at":"2024-01-21T02:18:44.702-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Toward_The_Development_Of_New_Drugs_For_Parasitic_Diseases","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"The international institute of Cellular and Molecular Pathology (ICP), which was founded in 1974 in Brussels by Christian de Duve, has as its specific aim to promote close collaboration between the basic and applied medical research fields and their application to medicine and therapeutics through the great achievements, technologies, and knowledge gained during the last 25 years in the field of basic cellular and molecular biology. Being an officially recognized WHO Collaborating Centre, the ICP has set itself two tasks: (1) to contribute to the development of entirely new drugs by increasing our still poor knowledge about the causative agents of tropical diseases and (2) to improve the efficacy of already existing drugs by developing vehicles capable of targeting these to the tissues and organs affected by the parasite.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":164,"name":"Parasitology","url":"https://www.academia.edu/Documents/in/Parasitology"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":3647879,"name":"Springer Ebooks","url":"https://www.academia.edu/Documents/in/Springer_Ebooks"}],"urls":[{"id":38775288,"url":"https://doi.org/10.1007/978-1-4612-5550-5_16"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809710"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809710/Aerobic_Protists_Trypanosomatidae"><img alt="Research paper thumbnail of Aerobic Protists—Trypanosomatidae" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809710/Aerobic_Protists_Trypanosomatidae">Aerobic Protists—Trypanosomatidae</a></div><div class="wp-workCard_item"><span>Elsevier eBooks</span><span>, 2003</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, pr...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809710"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809710"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809710; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809710]").text(description); $(".js-view-count[data-work-id=113809710]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809710; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809710']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809710, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809710]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809710,"title":"Aerobic Protists—Trypanosomatidae","translated_title":"","metadata":{"abstract":"Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.","publisher":"Elsevier BV","publication_date":{"day":null,"month":null,"year":2003,"errors":{}},"publication_name":"Elsevier eBooks"},"translated_abstract":"Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.","internal_url":"https://www.academia.edu/113809710/Aerobic_Protists_Trypanosomatidae","translated_internal_url":"","created_at":"2024-01-21T02:18:44.541-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Aerobic_Protists_Trypanosomatidae","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"Publisher Summary This chapter focuses on the carbohydrate metabolism of the Trypanosomatidae, protozoan parasites responsible for a number of important diseases of man. Many enzymes of glycolysis and related pathways in trypanosomatids are sequestered inside microbodies, which makes them usefulnot only as a drug target but also for basic research. The potential for chemotherapeutic exploitation of carbohydrate metabolism is significant. The biochemistry of trypanosomes is studied in great detail, because these organisms harbor many peculiarities that have attracted biochemists interested in fundamental aspects of these organisms. The fact that trypanosomes are among the few parasitic organisms that can easily be grown in large numbers in the blood of infected rodents has facilitated their study. The chapter concludes that the advent of molecular biology where the number of cells available for research is no longer a limiting factor, has led to an enormous growth of the literature over recent years. Through the combined efforts of many researchers in various disciplines over many years, a good understanding of the glycolytic pathway of the African trypanosome is obtained. These efforts have led to the cloning, sequencing, and over expression of all the enzymes of the pathway and the resolution of the crystal structure of many.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":375896,"name":"Trypanosoma","url":"https://www.academia.edu/Documents/in/Trypanosoma"},{"id":3983118,"name":"Molecular medical parasitology","url":"https://www.academia.edu/Documents/in/Molecular_medical_parasitology"}],"urls":[{"id":38775287,"url":"https://doi.org/10.1016/b978-012473346-6/50009-0"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809709"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809709/Biogenesis_and_Evolutionary_Origin_of_Peroxisomes"><img alt="Research paper thumbnail of Biogenesis and Evolutionary Origin of Peroxisomes" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809709/Biogenesis_and_Evolutionary_Origin_of_Peroxisomes">Biogenesis and Evolutionary Origin of Peroxisomes</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 1989</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most euka...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. They may have quite different functions within the eukaryotic cell (Lazarow and Fujiki, 1985; Huang et al, 1983; Opperdoes, 1987). Table 1 gives an overview of the principal metabolic pathways that have been found in microbodies. Despite such differences in function, it is now generally accepted that all these microbodies are members of one family of organelles. Morphologically, they have the same appearance. They are round or oval-shaped, but range in size from 0.2 to 1 micrometer. They are surrounded by a single membrane and have an electron-dense matrix, which sometimes contains a crystalloid inclusion (Fig. 1). They are found in almost all eukaryotic cells, such as protozoa, fungi, plants and animals. All microbodies have beta-oxidation as the common pathway. Peroxide metabolism, consisting of H202-producing oxidases and catalase, was originally thought to be the main characteristic of these organelles, since catalase is present in the microbodies of most organisms. However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809709"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809709"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809709; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809709]").text(description); $(".js-view-count[data-work-id=113809709]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809709; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809709']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809709, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=113809709]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809709,"title":"Biogenesis and Evolutionary Origin of Peroxisomes","translated_title":"","metadata":{"abstract":"In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. They may have quite different functions within the eukaryotic cell (Lazarow and Fujiki, 1985; Huang et al, 1983; Opperdoes, 1987). Table 1 gives an overview of the principal metabolic pathways that have been found in microbodies. Despite such differences in function, it is now generally accepted that all these microbodies are members of one family of organelles. Morphologically, they have the same appearance. They are round or oval-shaped, but range in size from 0.2 to 1 micrometer. They are surrounded by a single membrane and have an electron-dense matrix, which sometimes contains a crystalloid inclusion (Fig. 1). They are found in almost all eukaryotic cells, such as protozoa, fungi, plants and animals. All microbodies have beta-oxidation as the common pathway. Peroxide metabolism, consisting of H202-producing oxidases and catalase, was originally thought to be the main characteristic of these organelles, since catalase is present in the microbodies of most organisms. However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.","publisher":"Springer Nature","publication_date":{"day":null,"month":null,"year":1989,"errors":{}},"publication_name":"Springer eBooks"},"translated_abstract":"In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. They may have quite different functions within the eukaryotic cell (Lazarow and Fujiki, 1985; Huang et al, 1983; Opperdoes, 1987). Table 1 gives an overview of the principal metabolic pathways that have been found in microbodies. Despite such differences in function, it is now generally accepted that all these microbodies are members of one family of organelles. Morphologically, they have the same appearance. They are round or oval-shaped, but range in size from 0.2 to 1 micrometer. They are surrounded by a single membrane and have an electron-dense matrix, which sometimes contains a crystalloid inclusion (Fig. 1). They are found in almost all eukaryotic cells, such as protozoa, fungi, plants and animals. All microbodies have beta-oxidation as the common pathway. Peroxide metabolism, consisting of H202-producing oxidases and catalase, was originally thought to be the main characteristic of these organelles, since catalase is present in the microbodies of most organisms. However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.","internal_url":"https://www.academia.edu/113809709/Biogenesis_and_Evolutionary_Origin_of_Peroxisomes","translated_internal_url":"","created_at":"2024-01-21T02:18:44.355-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":32147726,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[],"slug":"Biogenesis_and_Evolutionary_Origin_of_Peroxisomes","translated_slug":"","page_count":null,"language":"en","content_type":"Work","summary":"In 1965 de Duve coined the name peroxisome for the microbody-like organelles present in most eukaryotic cells. Microbodies, as a group, are quite heterogeneous and comprise a variety of organelles such as peroxisomes, glyoxysomes and glycosomes. 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However, this ’marker enzyme’ may as well be absent as has been described in the case of the Euglenoids (Muller, 1975), the Trypanosomatids (Opperdoes, 1987) and some fungi (Kunau et al., 1987). Glyoxysomes, typical for germinating plants contain, in addition to the above mentioned pathways, enzymes of the glyoxylate cycle. Glycosomes, the microbodies typical of the Kinetoplastida - flagellated protozoa that comprise the parasitic trypanosomes, responsible for a number of important diseases of mankind - are highly specialised in glycolysis and contain the first seven enzymes of the Embden-Meyerhof pathway as well as two enzymes of glycerol metabolism. The peroxisomes of methylotrophic fungi and the fungi that grow on alkanes, are highly specialised in the oxidation of methanol and fatty acids, respectively.","owner":{"id":32147726,"first_name":"Fred","middle_initials":null,"last_name":"Opperdoes","page_name":"FredOpperdoes","domain_name":"uclouvain","created_at":"2015-06-12T23:19:33.639-07:00","display_name":"Fred Opperdoes","url":"https://uclouvain.academia.edu/FredOpperdoes"},"attachments":[],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":161099,"name":"Biogenesis","url":"https://www.academia.edu/Documents/in/Biogenesis"},{"id":534463,"name":"Peroxisome","url":"https://www.academia.edu/Documents/in/Peroxisome"},{"id":3647879,"name":"Springer Ebooks","url":"https://www.academia.edu/Documents/in/Springer_Ebooks"}],"urls":[{"id":38775286,"url":"https://doi.org/10.1007/978-1-4613-0545-3_13"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809707"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/113809707/Phylogenetic_analysis_using_protein_sequences"><img alt="Research paper thumbnail of Phylogenetic analysis using protein sequences" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/113809707/Phylogenetic_analysis_using_protein_sequences">Phylogenetic analysis using protein sequences</a></div><div class="wp-workCard_item"><span>Cambridge University Press eBooks</span><span>, Jun 17, 2012</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809707"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809707"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809707; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="113809706"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/113809706/Biogenesis_of_the_glycosome_in_Trypanosoma_brucei_the_synthesis_translocation_and_turnover_of_glycosomal_polypeptides"><img alt="Research paper thumbnail of Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides" class="work-thumbnail" src="https://attachments.academia-assets.com/110676170/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/113809706/Biogenesis_of_the_glycosome_in_Trypanosoma_brucei_the_synthesis_translocation_and_turnover_of_glycosomal_polypeptides">Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides</a></div><div class="wp-workCard_item"><span>The EMBO Journal</span><span>, May 1, 1987</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Communicated by C.de Duve Glycosomes, the microbodies of Trypanosoma brucei, contain a number of ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Communicated by C.de Duve Glycosomes, the microbodies of Trypanosoma brucei, contain a number of enzymes involved in glucose and glycerol metabolism. The biogenesis of three of these enzymes has been studied. Aldolase, D-glyceraldehyde-3-phosphate dehydrogenase and NAD-linked glycerol-3-phosphate dehydrogenase are all synthesized in the cytosol on free rather than on membrane-bound polysomes. In vitro, as well as in vivo, these polypeptides are synthesized at their mature size, and no evidence was found for any processing upon entry into the glycosomes. Continuous and pulse-chase labelling experiments with procyclic trypomastigotes revealed that the enzymes have a half-life in the cytosol of-3 min or less, and then turn over rapidly in the glycosomes, with half-lives as short as 30 min.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="9e8e28c2c0c42eb9c754ae3db3708cc3" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":110676170,"asset_id":113809706,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/110676170/download_file?st=MTczNjkzMjc1NSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="113809706"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="113809706"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 113809706; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=113809706]").text(description); $(".js-view-count[data-work-id=113809706]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 113809706; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='113809706']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 113809706, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "9e8e28c2c0c42eb9c754ae3db3708cc3" } } $('.js-work-strip[data-work-id=113809706]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":113809706,"title":"Biogenesis of the glycosome in Trypanosoma brucei: the synthesis, translocation and turnover of glycosomal polypeptides","translated_title":"","metadata":{"publisher":"Nature Portfolio","grobid_abstract":"Communicated by C.de Duve Glycosomes, the microbodies of Trypanosoma brucei, contain a number of enzymes involved in glucose and glycerol metabolism. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="107724686"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" rel="nofollow" href="https://www.academia.edu/107724686/The_Glycosome_of_Leishmania_as_a_Possible_Target_for_Chemotherapeutic_Attack"><img alt="Research paper thumbnail of The Glycosome of Leishmania as a Possible Target for Chemotherapeutic Attack" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" rel="nofollow" href="https://www.academia.edu/107724686/The_Glycosome_of_Leishmania_as_a_Possible_Target_for_Chemotherapeutic_Attack">The Glycosome of Leishmania as a Possible Target for Chemotherapeutic Attack</a></div><div class="wp-workCard_item"><span>Springer eBooks</span><span>, 1989</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Basic studies over the last ten years have revealed that all Try-panosomatidae harbour a number o...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Basic studies over the last ten years have revealed that all Try-panosomatidae harbour a number of biochemical features unique in Nature. 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