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N-linked glycosylation - Wikipedia

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href="https://bs.wikipedia.org/wiki/N-vezana_glikozilacija" title="N-vezana glikozilacija – Bosnian" lang="bs" hreflang="bs" data-title="N-vezana glikozilacija" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target"><span>Bosanski</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/N-Glykosylierung" title="N-Glykosylierung – German" lang="de" hreflang="de" data-title="N-Glykosylierung" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/N-glicosilaci%C3%B3n" title="N-glicosilación – Spanish" lang="es" hreflang="es" data-title="N-glicosilación" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/N-%DA%AF%D9%84%DB%8C%DA%A9%D9%88%D9%84%DB%8C%D8%B2%D8%A7%D8%B3%DB%8C%D9%88%D9%86" title="N-گلیکولیزاسیون – Persian" lang="fa" hreflang="fa" data-title="N-گلیکولیزاسیون" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/N-glycosylation" title="N-glycosylation – French" lang="fr" hreflang="fr" data-title="N-glycosylation" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/N-%EA%B2%B0%ED%95%A9_%EA%B8%80%EB%A6%AC%EC%BD%94%EC%8B%A4%ED%99%94" title="N-결합 글리코실화 – Korean" lang="ko" hreflang="ko" data-title="N-결합 글리코실화" data-language-autonym="한국어" data-language-local-name="Korean" 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src="//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Variety_of_glycans.svg/440px-Variety_of_glycans.svg.png" decoding="async" width="440" height="254" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Variety_of_glycans.svg/660px-Variety_of_glycans.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/a/a0/Variety_of_glycans.svg/880px-Variety_of_glycans.svg.png 2x" data-file-width="900" data-file-height="520" /></a><figcaption>The different types of <b>lipid-linked oligosaccharide</b> (LLO) precursor produced in different organisms.</figcaption></figure> <p><b><i>N</i>-linked glycosylation</b> is the attachment of an <a href="/wiki/Oligosaccharide" title="Oligosaccharide">oligosaccharide</a>, a carbohydrate consisting of several sugar molecules, sometimes also referred to as <a href="/wiki/Glycan" title="Glycan">glycan</a>, to a nitrogen atom (the <a href="/wiki/Amide" title="Amide">amide</a> nitrogen of an <a href="/wiki/Asparagine" title="Asparagine">asparagine</a> (Asn) residue of a <a href="/wiki/Protein" title="Protein">protein</a>), in a process called <b><i>N</i>-glycosylation</b>, studied in <a href="/wiki/Biochemistry" title="Biochemistry">biochemistry</a>.<sup id="cite_ref-1" class="reference"><a href="#cite_note-1"><span class="cite-bracket">&#91;</span>1<span class="cite-bracket">&#93;</span></a></sup> The resulting protein is called an <b>N-linked glycan</b>, or simply an <b>N-glycan</b>. </p><p>This type of linkage is important for both the structure<sup id="cite_ref-Imperiali_1999_2-0" class="reference"><a href="#cite_note-Imperiali_1999-2"><span class="cite-bracket">&#91;</span>2<span class="cite-bracket">&#93;</span></a></sup> and function<sup id="cite_ref-Patterson_20056_3-0" class="reference"><a href="#cite_note-Patterson_20056-3"><span class="cite-bracket">&#91;</span>3<span class="cite-bracket">&#93;</span></a></sup> of many eukaryotic proteins. The <i>N</i>-linked <a href="/wiki/Glycosylation" title="Glycosylation">glycosylation</a> process occurs in <a href="/wiki/Eukaryotes" class="mw-redirect" title="Eukaryotes">eukaryotes</a> and widely in <a href="/wiki/Archaea" title="Archaea">archaea</a>, but very rarely in <a href="/wiki/Bacteria" title="Bacteria">bacteria</a>. The nature of <i>N</i>-linked glycans attached to a glycoprotein is determined by the protein and the cell in which it is expressed.<sup id="cite_ref-Drickamer_2006_4-0" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> It also varies across <a href="/wiki/Species" title="Species">species</a>. Different species synthesize different types of <i>N</i>-linked glycan. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Energetics_of_bond_formation">Energetics of bond formation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=1" title="Edit section: Energetics of bond formation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>There are two types of bonds involved in a glycoprotein: bonds between the <a href="/wiki/Saccharides" class="mw-redirect" title="Saccharides">saccharides</a> residues in the glycan and the linkage between the glycan chain and the protein molecule. </p><p>The sugar <a href="/wiki/Moiety_(chemistry)" title="Moiety (chemistry)">moieties</a> are linked to one another in the glycan chain via <a href="/wiki/Glycosidic_bonds" class="mw-redirect" title="Glycosidic bonds">glycosidic bonds</a>. These bonds are typically formed between <a href="/wiki/Carbon" title="Carbon">carbons</a> 1 and 4 of the sugar molecules. The formation of glycosidic bond is energetically unfavourable, therefore the reaction is coupled to the <a href="/wiki/Hydrolysis" title="Hydrolysis">hydrolysis</a> of two <a href="/wiki/Adenosine_triphosphate" title="Adenosine triphosphate">ATP</a> molecules.<sup id="cite_ref-Drickamer_2006_4-1" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p><p>On the other hand, the attachment of a glycan residue to a protein requires the recognition of a <a href="/wiki/Consensus_sequence" title="Consensus sequence">consensus sequence</a>. <i>N</i>-linked glycans are almost always attached to the <a href="/wiki/Nitrogen" title="Nitrogen">nitrogen</a> atom of an asparagine (Asn) side chain that is present as a part of Asn–X–<a href="/wiki/Serine" title="Serine">Ser</a>/<a href="/wiki/Threonine" title="Threonine">Thr</a> consensus sequence, where X is any amino acid except <a href="/wiki/Proline" title="Proline">proline</a> (Pro).<sup id="cite_ref-Drickamer_2006_4-2" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p><p>In animal cells, the glycan attached to the asparagine is almost inevitably <a href="/wiki/N-Acetylglucosamine" title="N-Acetylglucosamine"><i>N</i>-acetylglucosamine</a> (GlcNAc) in the β-configuration.<sup id="cite_ref-Drickamer_2006_4-3" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> This β-linkage is similar to glycosidic bond between the sugar moieties in the glycan structure as described above. Instead of being attached to a sugar <a href="/wiki/Hydroxyl" class="mw-redirect" title="Hydroxyl">hydroxyl</a> group, the <a href="/wiki/Anomeric_carbon" class="mw-redirect" title="Anomeric carbon">anomeric carbon</a> atom is attached to an amide nitrogen. The energy required for this linkage comes from the <a href="/wiki/Hydrolysis" title="Hydrolysis">hydrolysis</a> of a <a href="/wiki/Pyrophosphate" title="Pyrophosphate">pyrophosphate</a> molecule.<sup id="cite_ref-Drickamer_2006_4-4" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Biosynthesis">Biosynthesis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=2" title="Edit section: Biosynthesis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Biosynthesis_of_N-glycan.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/b4/Biosynthesis_of_N-glycan.svg/440px-Biosynthesis_of_N-glycan.svg.png" decoding="async" width="440" height="246" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/b4/Biosynthesis_of_N-glycan.svg/660px-Biosynthesis_of_N-glycan.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/b4/Biosynthesis_of_N-glycan.svg/880px-Biosynthesis_of_N-glycan.svg.png 2x" data-file-width="1330" data-file-height="744" /></a><figcaption>Biosynthesis pathway of <i>N</i>-linked glycoproteins: The synthesis of <i>N</i>-linked glycan starts in the endoplasmic reticulum, continues in the Golgi and ends at the plasma membrane, where the <i>N</i>-linked glycoproteins are either secreted or becomes embedded in the plasma membrane.</figcaption></figure> <p>The biosynthesis of <i>N</i>-linked glycans occurs via three major steps:<sup id="cite_ref-Drickamer_2006_4-5" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p> <ol><li>Synthesis of dolichol-linked precursor oligosaccharide</li> <li>En bloc transfer of precursor oligosaccharide to protein</li> <li>Processing of the oligosaccharide</li></ol> <p>Synthesis, en bloc transfer and initial trimming of precursor <a href="/wiki/Oligosaccharide" title="Oligosaccharide">oligosaccharide</a> occurs in the <a href="/wiki/Endoplasmic_reticulum" title="Endoplasmic reticulum">endoplasmic reticulum</a> (ER). Subsequent processing and modification of the oligosaccharide chain are carried out in the <a href="/wiki/Golgi_apparatus" title="Golgi apparatus">Golgi apparatus</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (December 2024)">citation needed</span></a></i>&#93;</sup> </p><p>The synthesis of glycoproteins is thus spatially separated in different cellular compartments. Therefore, the type of <i>N</i>-glycan synthesized, depends on its accessibility to the different enzymes present within these cellular compartments.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (December 2024)">citation needed</span></a></i>&#93;</sup> </p><p>However, in spite of the diversity, all <i>N</i>-glycans are synthesized through a <a href="/wiki/Undecaprenyl_phosphate_N,N%27-diacetylbacillosamine_1-phosphate_transferase" title="Undecaprenyl phosphate N,N&#39;-diacetylbacillosamine 1-phosphate transferase">common pathway</a> with a common core glycan structure.<sup id="cite_ref-Drickamer_2006_4-6" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> The core glycan structure is essentially made up of two <i>N</i>-acetyl glucosamine and three <a href="/wiki/Mannose" title="Mannose">mannose</a> residues. This core glycan is then elaborated and modified further, resulting in a diverse range of <i>N</i>-glycan structures.<sup id="cite_ref-Drickamer_2006_4-7" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Synthesis_of_precursor_oligosaccharide">Synthesis of precursor oligosaccharide</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=3" title="Edit section: Synthesis of precursor oligosaccharide"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The process of <i>N</i>-linked glycosylation starts with the formation of <a href="/wiki/Dolichol" title="Dolichol">dolichol</a>-linked GlcNAc sugar. Dolichol is a <a href="/wiki/Lipid" title="Lipid">lipid</a> molecule composed of repeating <a href="/wiki/Isoprene" title="Isoprene">isoprene</a> units. This molecule is found attached to the membrane of the ER. Sugar molecules are attached to the dolichol through a pyrophosphate linkage<sup id="cite_ref-Drickamer_2006_4-8" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> (one <a href="/wiki/Phosphate" title="Phosphate">phosphate</a> was originally linked to dolichol, and the second phosphate came from the <a href="/wiki/Nucleotide" title="Nucleotide">nucleotide</a> sugar). The oligosaccharide chain is then extended through the addition of various sugar molecules in a stepwise manner to form a precursor oligosaccharide.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (December 2024)">citation needed</span></a></i>&#93;</sup> </p><p>The assembly of this precursor oligosaccharide occurs in two phases: Phase I and II.<sup id="cite_ref-Drickamer_2006_4-9" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> Phase I takes place on the <a href="/wiki/Cytoplasmic" class="mw-redirect" title="Cytoplasmic">cytoplasmic</a> side of the ER and Phase II takes place on the <a href="/wiki/Lumen_(anatomy)" title="Lumen (anatomy)">luminal</a> side of the ER.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (December 2024)">citation needed</span></a></i>&#93;</sup> </p><p>The precursor molecule, ready to be transferred to a protein, consists of two GlcNAc, nine mannose, and three <a href="/wiki/Glucose" title="Glucose">glucose</a> molecules. </p> <figure class="mw-default-size mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:N-glycan_precursor_synthesis_in_the_ER_lumen.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/4/4b/N-glycan_precursor_synthesis_in_the_ER_lumen.png/350px-N-glycan_precursor_synthesis_in_the_ER_lumen.png" decoding="async" width="350" height="326" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/4/4b/N-glycan_precursor_synthesis_in_the_ER_lumen.png/525px-N-glycan_precursor_synthesis_in_the_ER_lumen.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/4/4b/N-glycan_precursor_synthesis_in_the_ER_lumen.png/700px-N-glycan_precursor_synthesis_in_the_ER_lumen.png 2x" data-file-width="2933" data-file-height="2728" /></a><figcaption>Step-by-step synthesis of the precursor oligosaccharide in the ER lumen during <i>N</i>-linked glycosylation: the diagram illustrates the steps occurring in both the Phase I and Phase II as described in the table.</figcaption></figure> <table class="wikitable"> <tbody><tr> <th colspan="2"><div class="center" style="width:auto; margin-left:auto; margin-right:auto;"> Phase I </div> </th></tr> <tr> <th><div class="center" style="width:auto; margin-left:auto; margin-right:auto;"> Steps </div></th> <th><div class="center" style="width:auto; margin-left:auto; margin-right:auto;"> Location </div> </th></tr> <tr> <td> <div class="center"> <ul><li>Two <a href="/wiki/UDP-GlcNAc" class="mw-redirect" title="UDP-GlcNAc">UDP-GlcNAc</a> residues are attached to the dolichol molecule embedded in the ER membrane. The sugar and dolichol form a pyrophosphate linkage.</li> <li>Five <a href="/wiki/GDP-Man" class="mw-redirect" title="GDP-Man">GDP-Man</a> residues are attached to the GlcNAc <a href="/wiki/Disaccharide" title="Disaccharide">disaccharide</a>. These steps are performed by <a href="/wiki/Glycosyltransferases" class="mw-redirect" title="Glycosyltransferases">glycosyltransferases</a>.</li> <li>Product: Dolichol–GlcNAc<sub>2</sub>–Man<sub>5</sub> </li></ul></div> </td> <td> <div class="center" style="width:auto; margin-left:auto; margin-right:auto;"> Cytoplasmic side of ER </div> </td></tr> <tr> <td colspan="2"> <div class="center"> At this point, the lipid-linked glycan is <a href="/wiki/Protein_translocation" class="mw-redirect" title="Protein translocation">translocated</a> across the membrane making it accessible to enzymes in the endoplasmic reticulum lumen. This translocation process is still poorly understood, but it is suggested to be performed by an enzyme known as <a href="/wiki/Flippase" title="Flippase">flippase</a>.</div> </td></tr> <tr> <th colspan="2">Phase II </th></tr> <tr> <td> <div class="center"> <ul><li>The growing glycan is exposed on the luminal side of the ER membrane and subsequent sugars (four mannose and three glucose) are added. Dol-P-Man is the Mannose residue donor (formation: Dol-P + GDP-Man → Dol-P-Man + GDP) and Dol-P-Gluc is the glucose residue donor (formation&#160;: Dol-P + UDP-Glc → Dol-P-Glc + UDP).</li> <li>These additional sugars are transported into the lumen of the ER from the cytoplasm via attachment to the dolichol molecule and subsequent translocation into the lumen with the help of flippase enzyme. (Various dolichols in the membrane are used to translocate multiple sugars at once).</li> <li>Product: Dolichol–GlcNAc<sub>2</sub>–Man<sub>9</sub>–Glc<sub>3</sub> </li></ul></div> </td> <td><div class="center" style="width:auto; margin-left:auto; margin-right:auto;"> Luminal side of ER </div> </td></tr></tbody></table> <div class="mw-heading mw-heading3"><h3 id="Transfer_of_glycan_to_protein">Transfer of glycan to protein</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=4" title="Edit section: Transfer of glycan to protein"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Once the precursor oligosaccharide is formed, the completed glycan is then transferred to the nascent <a href="/wiki/Polypeptide" class="mw-redirect" title="Polypeptide">polypeptide</a> in the lumen of the ER membrane. This reaction is driven by the energy released from the cleavage of the pyrophosphate bond between the dolichol-glycan molecule. There are three conditions to fulfill before a glycan is transferred to a nascent polypeptide:<sup id="cite_ref-Drickamer_2006_4-10" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p> <ul><li>Asparagine must be located in a specific consensus sequence in the <a href="/wiki/Primary_structure" class="mw-redirect" title="Primary structure">primary structure</a> (Asn–X–Ser or Asn–X–Thr or in rare instances Asn–X–Cys).<sup id="cite_ref-Mellquist_1998_5-0" class="reference"><a href="#cite_note-Mellquist_1998-5"><span class="cite-bracket">&#91;</span>5<span class="cite-bracket">&#93;</span></a></sup></li> <li>Asparagine must be located appropriately in the three-dimensional structure of the protein (Sugars are <a href="/wiki/Polar_molecules" class="mw-redirect" title="Polar molecules">polar molecules</a> and thus need to be attached to asparagine located on the surface of the protein and not buried within the protein)</li> <li>Asparagine must be found in the luminal side of the endoplasmic reticulum for <i>N</i>-linked glycosylation to be initiated. Target residues are either found in secretory proteins or in the regions of <a href="/wiki/Transmembrane_protein" title="Transmembrane protein">transmembrane protein</a> that face the lumen.</li></ul> <p><a href="/wiki/Oligosaccharyltransferase" title="Oligosaccharyltransferase">Oligosaccharyltransferase</a> is the enzyme responsible for the recognition of the consensus sequence and the transfer of the precursor glycan to a polypeptide acceptor which is being translated in the endoplasmic reticulum lumen. <i>N</i>-linked glycosylation is, therefore, a co-translational event.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (December 2024)">citation needed</span></a></i>&#93;</sup> </p> <div class="mw-heading mw-heading3"><h3 id="Processing_of_glycan">Processing of glycan</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=5" title="Edit section: Processing of glycan"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-left" typeof="mw:File/Thumb"><a href="/wiki/File:Glycan_processing_in_the_ER_and_Golgi.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/1/11/Glycan_processing_in_the_ER_and_Golgi.png/440px-Glycan_processing_in_the_ER_and_Golgi.png" decoding="async" width="440" height="281" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/1/11/Glycan_processing_in_the_ER_and_Golgi.png/660px-Glycan_processing_in_the_ER_and_Golgi.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/1/11/Glycan_processing_in_the_ER_and_Golgi.png/880px-Glycan_processing_in_the_ER_and_Golgi.png 2x" data-file-width="4438" data-file-height="2830" /></a><figcaption>Glycan processing in the ER and Golgi.</figcaption></figure> <p><i>N</i>-glycan processing is carried out in endoplasmic reticulum and the Golgi body. Initial trimming of the precursor molecule occurs in the ER and the subsequent processing occurs in the Golgi. </p><p>Upon transferring the completed glycan onto the nascent polypeptide, two glucose residues are removed from the structure. Enzymes known as glycosidases remove some sugar residues. These enzymes can break glycosidic linkages by using a water molecule. These enzymes are exoglycosidases as they only work on <a href="/wiki/Monosaccharide" title="Monosaccharide">monosaccharide</a> residues located at the non-reducing end of the glycan.<sup id="cite_ref-Drickamer_2006_4-11" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> This initial trimming step is thought to act as a quality control step in the ER to monitor <a href="/wiki/Protein_folding" title="Protein folding">protein folding</a>. </p><p>Once the protein is folded correctly, two glucose residues are removed by <a href="/wiki/Glucosidase" class="mw-redirect" title="Glucosidase">glucosidase</a> I and II. The removal of the final third glucose residue signals that the glycoprotein is ready for transit from the ER to the <i>cis</i>-Golgi.<sup id="cite_ref-Drickamer_2006_4-12" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> ER mannosidase catalyses the removal of this final glucose. However, if the protein is not folded properly, the glucose residues are not removed and thus the glycoprotein can't leave the endoplasmic reticulum. A <a href="/wiki/Chaperone_(protein)" title="Chaperone (protein)">chaperone</a> protein (<a href="/wiki/Calnexin" title="Calnexin">calnexin</a>/<a href="/wiki/Calreticulin" title="Calreticulin">calreticulin</a>) binds to the unfolded or partially folded protein to assist protein folding. </p><p>The next step involves further addition and removal of sugar residues in the cis-Golgi. These modifications are catalyzed by glycosyltransferases and glycosidases respectively. In the <i>cis</i>-Golgi, a series of mannosidases remove some or all of the four mannose residues in α-1,2 linkages.<sup id="cite_ref-Drickamer_2006_4-13" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> Whereas in the medial portion of the Golgi, glycosyltransferases add sugar residues to the core glycan structure, giving rise to the three main types of glycans: high mannose, hybrid and complex glycans. </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Types_of_glycans.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Types_of_glycans.svg/310px-Types_of_glycans.svg.png" decoding="async" width="310" height="194" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Types_of_glycans.svg/465px-Types_of_glycans.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Types_of_glycans.svg/620px-Types_of_glycans.svg.png 2x" data-file-width="800" data-file-height="500" /></a><figcaption>The three major types of glycans.</figcaption></figure> <ul><li>High-mannose is, in essence, just two <i>N</i>-acetylglucosamines with many mannose residues, often almost as many as are seen in the precursor oligosaccharides before it is attached to the protein.</li> <li>Complex oligosaccharides are so named because they can contain almost any number of the other types of saccharides, including more than the original two <i>N</i>-acetylglucosamines.</li> <li>Hybrid oligosaccharides contain a mannose residues on one side of the branch, while on the other side a <i>N</i>-acetylglucosamine initiates a complex branch.</li></ul> <p>The order of addition of sugars to the growing glycan chains is determined by the substrate specificities of the enzymes and their access to the substrate as they move through <a href="/wiki/Secretory_pathway" class="mw-redirect" title="Secretory pathway">secretory pathway</a>. Thus, the organization of this machinery within a cell plays an important role in determining which glycans are made.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">&#91;<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (December 2024)">citation needed</span></a></i>&#93;</sup> </p> <div class="mw-heading mw-heading4"><h4 id="Enzymes_in_the_Golgi">Enzymes in the Golgi</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=6" title="Edit section: Enzymes in the Golgi"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Golgi enzymes play a key role in determining the synthesis of the various types of glycans. The order of action of the enzymes is reflected in their position in the Golgi stack: </p> <table class="wikitable"> <tbody><tr> <th>Enzymes</th> <th>Location within Golgi </th></tr> <tr> <td>Mannosidase I</td> <td><i>cis</i>-Golgi </td></tr> <tr> <td>GlcNAc transferases</td> <td>medial Golgi </td></tr> <tr> <td><a href="/wiki/Galactosyltransferase" title="Galactosyltransferase">Galactosyltransferase</a> and <a href="/wiki/Sialyltransferase" title="Sialyltransferase">Sialyltransferase</a></td> <td><i>trans</i>-Golgi </td></tr></tbody></table> <div class="mw-heading mw-heading3"><h3 id="In_archaea_and_prokaryotes">In archaea and prokaryotes</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=7" title="Edit section: In archaea and prokaryotes"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Similar <i>N</i>-glycan biosynthesis pathway have been found in prokaryotes and Archaea.<sup id="cite_ref-Klaus_1977_6-0" class="reference"><a href="#cite_note-Klaus_1977-6"><span class="cite-bracket">&#91;</span>6<span class="cite-bracket">&#93;</span></a></sup> However, compared to eukaryotes, the final glycan structure in eubacteria and archaea does not seem to differ much from the initial precursor made in the endoplasmic reticulum. In eukaryotes, the original precursor oligosaccharide is extensively modified en route to the cell surface.<sup id="cite_ref-Drickamer_2006_4-14" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Function">Function</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=8" title="Edit section: Function"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><i>N</i>-linked glycans have intrinsic and extrinsic functions.<sup id="cite_ref-Drickamer_2006_4-15" class="reference"><a href="#cite_note-Drickamer_2006-4"><span class="cite-bracket">&#91;</span>4<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">&#91;</span>7<span class="cite-bracket">&#93;</span></a></sup> </p><p>Within the immune system, the <i>N</i>-linked glycans on an immune cell's surface will help dictate that migration pattern of the cell, e.g. immune cells that migrate to the skin have specific glycosylations that favor homing to that site.<sup id="cite_ref-Maverakis_2015_8-0" class="reference"><a href="#cite_note-Maverakis_2015-8"><span class="cite-bracket">&#91;</span>8<span class="cite-bracket">&#93;</span></a></sup> The glycosylation patterns on the various immunoglobulins including IgE, IgM, IgD, IgA, and IgG bestow them with unique effector functions by altering their affinities for Fc and other immune receptors.<sup id="cite_ref-Maverakis_2015_8-1" class="reference"><a href="#cite_note-Maverakis_2015-8"><span class="cite-bracket">&#91;</span>8<span class="cite-bracket">&#93;</span></a></sup> Glycans may also be involved in "self" and "non self" discrimination, which may be relevant to the pathophysiology of various autoimmune diseases.<sup id="cite_ref-Maverakis_2015_8-2" class="reference"><a href="#cite_note-Maverakis_2015-8"><span class="cite-bracket">&#91;</span>8<span class="cite-bracket">&#93;</span></a></sup> </p> <table class="wikitable"> <caption>Functions of <i>N</i>-linked glycans </caption> <tbody><tr> <td>Intrinsic</td> <td> <ol><li>Provides structural components to the cell wall and extracellular matrix.</li> <li>Modify protein properties such as stability and solubility<sup id="cite_ref-Sinclair_2005_9-0" class="reference"><a href="#cite_note-Sinclair_2005-9"><span class="cite-bracket">&#91;</span>9<span class="cite-bracket">&#93;</span></a></sup> (more stable to high temperature, pH, etc.).</li> <li>Protects proteins against aggregation.<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">&#91;</span>10<span class="cite-bracket">&#93;</span></a></sup></li></ol> </td></tr> <tr> <td>Extrinsic</td> <td> <ol><li>Directs trafficking of glycoproteins.</li> <li>Mediates cell signalling (cell–cell and cell–matrix interactions).</li></ol> </td></tr></tbody></table> <p>In some cases, interaction between the N-glycan and the protein stabilizes the protein through complex electronic effects.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">&#91;</span>11<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Clinical_significance">Clinical significance</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=9" title="Edit section: Clinical significance"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Changes in <i>N</i>-linked glycosylation has been associated with different diseases including <a href="/wiki/Rheumatoid_arthritis" title="Rheumatoid arthritis">rheumatoid arthritis</a>,<sup id="cite_ref-Nakagawa_2007_12-0" class="reference"><a href="#cite_note-Nakagawa_2007-12"><span class="cite-bracket">&#91;</span>12<span class="cite-bracket">&#93;</span></a></sup> <a href="/wiki/Type_1_diabetes" title="Type 1 diabetes">type 1 diabetes</a>,<sup id="cite_ref-Bermingham_2018_13-0" class="reference"><a href="#cite_note-Bermingham_2018-13"><span class="cite-bracket">&#91;</span>13<span class="cite-bracket">&#93;</span></a></sup> <a href="/wiki/Crohn%27s_disease" title="Crohn&#39;s disease">Crohn's disease</a>,<sup id="cite_ref-Trbojević_2015_14-0" class="reference"><a href="#cite_note-Trbojević_2015-14"><span class="cite-bracket">&#91;</span>14<span class="cite-bracket">&#93;</span></a></sup> and cancers.<sup id="cite_ref-Kodar_2012_15-0" class="reference"><a href="#cite_note-Kodar_2012-15"><span class="cite-bracket">&#91;</span>15<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-Chen_2013_16-0" class="reference"><a href="#cite_note-Chen_2013-16"><span class="cite-bracket">&#91;</span>16<span class="cite-bracket">&#93;</span></a></sup> </p><p>Mutations in eighteen genes involved in <i>N</i>-linked glycosylation result in a variety of diseases, most of which involve the <a href="/wiki/Nervous_system" title="Nervous system">nervous system</a>.<sup id="cite_ref-Patterson_20056_3-1" class="reference"><a href="#cite_note-Patterson_20056-3"><span class="cite-bracket">&#91;</span>3<span class="cite-bracket">&#93;</span></a></sup><sup id="cite_ref-Chen_2013_16-1" class="reference"><a href="#cite_note-Chen_2013-16"><span class="cite-bracket">&#91;</span>16<span class="cite-bracket">&#93;</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Importance_in_therapeutic_proteins">Importance in therapeutic proteins</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=10" title="Edit section: Importance in therapeutic proteins"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Many <a href="/wiki/Therapeutic" class="mw-redirect" title="Therapeutic">therapeutic</a> proteins in the market are <a href="/wiki/Antibody" title="Antibody">antibodies</a>, which are <i>N</i>-linked glycoproteins. For example, <a href="/wiki/Etanercept" title="Etanercept">Etanercept</a>, <a href="/wiki/Infliximab" title="Infliximab">Infliximab</a> and <a href="/wiki/Rituximab" title="Rituximab">Rituximab</a> are <i>N</i>-glycosylated therapeutic proteins. </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Difference_between_animal_and_human.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/3/39/Difference_between_animal_and_human.svg/220px-Difference_between_animal_and_human.svg.png" decoding="async" width="220" height="151" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/39/Difference_between_animal_and_human.svg/330px-Difference_between_animal_and_human.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/39/Difference_between_animal_and_human.svg/440px-Difference_between_animal_and_human.svg.png 2x" data-file-width="744" data-file-height="510" /></a><figcaption>The difference between the glycan produced by humans and animal cells. Human cells lack the Neu5Gc cap.</figcaption></figure> <p>The importance of <i>N</i>-linked glycosylation is becoming increasingly evident in the field of <a href="/wiki/Pharmaceuticals" class="mw-redirect" title="Pharmaceuticals">pharmaceuticals</a>.<sup id="cite_ref-Dalziel_2014_17-0" class="reference"><a href="#cite_note-Dalziel_2014-17"><span class="cite-bracket">&#91;</span>17<span class="cite-bracket">&#93;</span></a></sup> Although bacterial or yeast <a href="/wiki/Protein_production" title="Protein production">protein production</a> systems have significant potential advantages such as high yield and low cost, problems arise when the protein of interest is a glycoprotein. Most prokaryotic expression systems such as <i><a href="/wiki/E._coli" class="mw-redirect" title="E. coli">E. coli</a></i> cannot carry out <a href="/wiki/Post-translational_modifications" class="mw-redirect" title="Post-translational modifications">post-translational modifications</a>. On the other hand, eukaryotic expression hosts such as yeast and animal cells, have different glycosylation patterns. The proteins produced in these expression hosts are often not identical to human protein and thus, cause <a href="/wiki/Immunogenic" class="mw-redirect" title="Immunogenic">immunogenic</a> reactions in patients. For example, <i><a href="/wiki/S.cerevisiae" class="mw-redirect" title="S.cerevisiae">S.cerevisiae</a></i> (yeast) often produce high-mannose glycans which are immunogenic. </p><p>Non-human mammalian expression systems such as <a href="/wiki/Chinese_hamster_ovary_cell" title="Chinese hamster ovary cell">CHO</a> or <a href="/wiki/NS0_cell" title="NS0 cell">NS0 cells</a> have the machinery required to add complex, human-type glycans. However, glycans produced in these systems can differ from glycans produced in humans, as they can be capped with both <a href="/wiki/N-glycolylneuraminic_acid" class="mw-redirect" title="N-glycolylneuraminic acid"><i>N</i>-glycolylneuraminic acid</a> (Neu5Gc) and <a href="/wiki/N-acetylneuraminic_acid" class="mw-redirect" title="N-acetylneuraminic acid"><i>N</i>-acetylneuraminic acid</a> (Neu5Ac), whereas human cells only produce glycoproteins containing <i>N</i>-acetylneuraminic acid. Furthermore, animal cells can also produce glycoproteins containing the <a href="/wiki/Galactose-alpha-1,3-galactose" class="mw-redirect" title="Galactose-alpha-1,3-galactose">galactose-alpha-1,3-galactose</a> epitope, which can induce serious allergenic reactions, including <a href="/wiki/Anaphylactic_shock" class="mw-redirect" title="Anaphylactic shock">anaphylactic shock</a>, in people who have <a href="/wiki/Alpha-gal_allergy" class="mw-redirect" title="Alpha-gal allergy">Alpha-gal allergy</a>. </p><p>These drawbacks have been addressed by several approaches such as eliminating the pathways that produce these glycan structures through genetic knockouts. Furthermore, other expression systems have been genetically engineered to produce therapeutic glycoproteins with human-like <i>N</i>-linked glycans. These include yeasts such as <i><a href="/wiki/Pichia_pastoris" class="mw-redirect" title="Pichia pastoris">Pichia pastoris</a></i>,<sup id="cite_ref-Hamilton_2003_18-0" class="reference"><a href="#cite_note-Hamilton_2003-18"><span class="cite-bracket">&#91;</span>18<span class="cite-bracket">&#93;</span></a></sup> insect cell lines, green plants,<sup id="cite_ref-Strasser_2014_19-0" class="reference"><a href="#cite_note-Strasser_2014-19"><span class="cite-bracket">&#91;</span>19<span class="cite-bracket">&#93;</span></a></sup> and even bacteria. </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=11" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Glycosylation" title="Glycosylation">Glycosylation</a></li> <li><a href="/wiki/O-linked_glycosylation" title="O-linked glycosylation"><i>O</i>-linked glycosylation</a></li> <li><a href="/wiki/Gene_expression" title="Gene expression">Gene expression</a></li> <li><a href="/wiki/N-glycosyltransferase" title="N-glycosyltransferase"><i>N</i>-Glycosyltransferase</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=12" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 32em;"> <ol class="references"> <li id="cite_note-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-1">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite class="citation web cs1"><a rel="nofollow" class="external text" href="https://www.uniprot.org/manual/carbohyd">"Glycosylation"</a>. <i>UniProt: Protein sequence and functional information</i>.</cite><span title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=unknown&amp;rft.jtitle=UniProt%3A+Protein+sequence+and+functional+information&amp;rft.atitle=Glycosylation&amp;rft_id=https%3A%2F%2Fwww.uniprot.org%2Fmanual%2Fcarbohyd&amp;rfr_id=info%3Asid%2Fen.wikipedia.org%3AN-linked+glycosylation" class="Z3988"></span></span> </li> <li id="cite_note-Imperiali_1999-2"><span class="mw-cite-backlink"><b><a href="#cite_ref-Imperiali_1999_2-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFImperialiO&#39;Connor1999" class="citation journal cs1">Imperiali B, O'Connor SE (December 1999). 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"Controlled glycosylation of plant-produced recombinant proteins". <i>Current Opinion in Biotechnology</i>. <b>30</b>: <span class="nowrap">95–</span>100. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.copbio.2014.06.008">10.1016/j.copbio.2014.06.008</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a>&#160;<a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/25000187">25000187</a>.</cite><span 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href="/wiki/Template:Metabolism" title="Template:Metabolism"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Metabolism" title="Template talk:Metabolism"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Metabolism" title="Special:EditPage/Template:Metabolism"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Metabolism,_catabolism,_anabolism113" style="font-size:114%;margin:0 4em"><a href="/wiki/Metabolism" title="Metabolism">Metabolism</a>, <a href="/wiki/Catabolism" title="Catabolism">catabolism</a>, <a href="/wiki/Anabolism" title="Anabolism">anabolism</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">General</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Metabolic_pathway" title="Metabolic pathway">Metabolic pathway</a></li> <li><a href="/wiki/Metabolic_network" title="Metabolic network">Metabolic network</a></li> <li><a href="/wiki/Primary_nutritional_groups" title="Primary nutritional groups">Primary nutritional groups</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Bioenergetics" title="Bioenergetics">Energy<br /> metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Aerobic_respiration" class="mw-redirect" title="Aerobic respiration">Aerobic respiration</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycolysis" title="Glycolysis">Glycolysis</a> → <a href="/wiki/Pyruvate_dehydrogenase" title="Pyruvate dehydrogenase">Pyruvate decarboxylation</a> → <a href="/wiki/Citric_acid_cycle" title="Citric acid cycle">Citric acid cycle</a> → <a href="/wiki/Oxidative_phosphorylation" title="Oxidative phosphorylation">Oxidative phosphorylation</a> (<span style="font-size:85%;"><a href="/wiki/Electron_transport_chain" title="Electron transport chain">electron transport chain</a> + <a href="/wiki/ATP_synthase" title="ATP synthase">ATP synthase</a></span>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Anaerobic_respiration" title="Anaerobic respiration">Anaerobic respiration</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Electron acceptors other than oxygen</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Fermentation" title="Fermentation">Fermentation</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycolysis" title="Glycolysis">Glycolysis</a> → <a href="/wiki/Substrate-level_phosphorylation" title="Substrate-level phosphorylation">Substrate-level phosphorylation</a> <ul><li><a href="/wiki/Acetone%E2%80%93butanol%E2%80%93ethanol_fermentation" title="Acetone–butanol–ethanol fermentation">ABE</a></li> <li><a href="/wiki/Ethanol_fermentation" title="Ethanol fermentation">Ethanol</a></li> <li><a href="/wiki/Lactic_acid_fermentation" title="Lactic acid fermentation">Lactic acid</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Specific<br /> paths</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Protein_metabolism" title="Protein metabolism">Protein metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Protein_biosynthesis" title="Protein biosynthesis">Protein synthesis</a></li> <li><a href="/wiki/Protein_catabolism" title="Protein catabolism">Catabolism</a> (protein→peptide→amino acid)</li></ul> </div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Amino_acid" title="Amino acid">Amino acid</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amino_acid_synthesis" title="Amino acid synthesis">Amino acid synthesis</a></li> <li><a href="/wiki/Protein_catabolism#Amino_acid_degradation" title="Protein catabolism">Amino acid degradation</a> (amino acid→pyruvate, acetyl CoA, or TCA intermediate)</li> <li><a href="/wiki/Urea_cycle" title="Urea cycle">Urea cycle</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Nucleic_acid_metabolism" title="Nucleic acid metabolism">Nucleotide<br /> metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Purine_metabolism" title="Purine metabolism">Purine metabolism</a></li> <li><a href="/wiki/Nucleotide_salvage" title="Nucleotide salvage">Nucleotide salvage</a></li> <li><a href="/wiki/Pyrimidine_metabolism" title="Pyrimidine metabolism">Pyrimidine metabolism</a></li> <li><a href="/wiki/Purine_nucleotide_cycle" title="Purine nucleotide cycle">Purine nucleotide cycle</a></li></ul> </div></td></tr></tbody></table><div> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Carbohydrate_metabolism" title="Carbohydrate metabolism">Carbohydrate metabolism</a><br />(<a href="/wiki/Carbohydrate_catabolism" title="Carbohydrate catabolism">carbohydrate catabolism</a><br />and <a href="/wiki/Anabolism" title="Anabolism">anabolism</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Human</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycolysis" title="Glycolysis">Glycolysis</a> ⇄ <a href="/wiki/Gluconeogenesis" title="Gluconeogenesis">Gluconeogenesis</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycogenolysis" title="Glycogenolysis">Glycogenolysis</a> ⇄ <a href="/wiki/Glycogenesis" title="Glycogenesis">Glycogenesis</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Pentose_phosphate_pathway" title="Pentose phosphate pathway">Pentose phosphate pathway</a></li> <li><a href="/wiki/Fructolysis" title="Fructolysis">Fructolysis</a> <ul><li><a href="/wiki/Polyol_pathway" title="Polyol pathway">Polyol pathway</a></li></ul></li> <li><a href="/wiki/Galactolysis" title="Galactolysis">Galactolysis</a> <ul><li><a href="/wiki/Leloir_pathway" title="Leloir pathway">Leloir pathway</a></li></ul></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycosylation" title="Glycosylation">Glycosylation</a> <ul><li><a class="mw-selflink selflink">N-linked</a></li> <li><a href="/wiki/O-linked_glycosylation" title="O-linked glycosylation">O-linked</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Nonhuman</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Photosynthesis" title="Photosynthesis">Photosynthesis</a></li> <li><a href="/wiki/Anoxygenic_photosynthesis" title="Anoxygenic photosynthesis">Anoxygenic photosynthesis</a></li> <li><a href="/wiki/Chemosynthesis" title="Chemosynthesis">Chemosynthesis</a></li> <li><a href="/wiki/Carbon_fixation" class="mw-redirect" title="Carbon fixation">Carbon fixation</a></li> <li><a href="/w/index.php?title=DeLey-Doudoroff_pathway&amp;action=edit&amp;redlink=1" class="new" title="DeLey-Doudoroff pathway (page does not exist)">DeLey-Doudoroff pathway</a></li> <li><a href="/wiki/Entner-Doudoroff_pathway" class="mw-redirect" title="Entner-Doudoroff pathway">Entner-Doudoroff pathway</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Xylose_metabolism" title="Xylose metabolism">Xylose metabolism</a></li> <li><a href="/wiki/Radiotrophic_fungus" title="Radiotrophic fungus">Radiotrophism</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Lipid_metabolism" title="Lipid metabolism">Lipid metabolism</a> <br />(<a href="/wiki/Lipolysis" title="Lipolysis">lipolysis</a>, <a href="/wiki/Lipogenesis" title="Lipogenesis">lipogenesis</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Fatty_acid_metabolism" title="Fatty acid metabolism">Fatty acid metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Fatty_acid_degradation" title="Fatty acid degradation">Fatty acid degradation</a> (<a href="/wiki/Beta_oxidation" title="Beta oxidation">Beta oxidation</a>)</li> <li><a href="/wiki/Fatty_acid_synthesis" title="Fatty acid synthesis">Fatty acid synthesis</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Steroid" title="Steroid">Steroid metabolism</a></li> <li><a href="/wiki/Sphingolipid_metabolism" class="mw-redirect" title="Sphingolipid metabolism">Sphingolipid metabolism</a></li> <li><a href="/wiki/Eicosanoid_metabolism" class="mw-redirect" title="Eicosanoid metabolism">Eicosanoid metabolism</a></li> <li><a href="/wiki/Ketosis" title="Ketosis">Ketosis</a></li> <li><a href="/wiki/Reverse_cholesterol_transport" title="Reverse cholesterol transport">Reverse cholesterol transport</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Bioinorganic_chemistry" title="Bioinorganic chemistry">Metal metabolism</a> <ul><li><a href="/wiki/Human_iron_metabolism" title="Human iron metabolism">Iron metabolism</a></li></ul></li> <li><a href="/wiki/Ethanol_metabolism" class="mw-redirect" title="Ethanol metabolism">Ethanol metabolism</a></li> <li><a href="/wiki/Phosphagen" title="Phosphagen">Phospagen system (ATP-PCr)</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=N-linked_glycosylation&amp;action=edit&amp;section=13" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a rel="nofollow" class="external text" href="http://crdd.osdd.net/raghava/glycoep/">GlycoEP</a>: In silico Platform for Prediction of <i>N</i>-, <i>O</i>- and <i>C</i>-Glycosites in Eukaryotic Protein Sequences</li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMaverakisKimShimodaGershwin2015" class="citation journal cs1">Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (February 2015). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340844">"Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review"</a>. <i>Journal of Autoimmunity</i>. <b>57</b>: <span class="nowrap">1–</span>13. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.jaut.2014.12.002">10.1016/j.jaut.2014.12.002</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a>&#160;<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340844">4340844</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a>&#160;<a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/25578468">25578468</a>.</cite><span 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