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<title>Pyruvatdehydrogenase E1</title>

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<h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">Pyruvatdehydrogenase E1</span></h1>

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<th colspan="3" style="background:#90EE90; color:#202122;">Pyruvatdehydrogenase E1

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<td colspan="3" class="hintergrundfarbe1" style="text-align:center; font-size:smaller; font-weight:bold;">Bändermodell des Tetramer nach <a href="Protein_Data_Bank" title="Protein Data Bank">PDB</a> <a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1NI4">1NI4</a>

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<p>Vorhandene Strukturdaten: <span class=""><a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/1ni4">1ni4</a></span>, <span class=""><a rel="nofollow" class="external text" href="https://www.rcsb.org/structure/2ozl">2ozl</a></span>

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<td><a href="Molare_Masse" title="Molare Masse">Masse</a>/Länge <a href="Prim%C3%A4rstruktur" title="Primärstruktur">Primärstruktur</a>

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<td colspan="2" style="text-align:center;">1380 = 2*361+2*329 Aminosäuren

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<td><a href="Sekund%C3%A4rstruktur" title="Sekundärstruktur">Sekundär-</a> bis <a href="Quart%C3%A4rstruktur" title="Quartärstruktur">Quartärstruktur</a>

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<td colspan="2" style="text-align:center;">2α+2β

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<td><a href="Koenzym" class="mw-redirect" title="Koenzym">Kofaktor</a>

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<td colspan="2" style="text-align:center;">Thiamindiphosphat

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<th colspan="3" style="background:#90EE90; color:#202122;">Bezeichner

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<td>Gen-Name(n)

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<th colspan="3" style="background:#90EE90; color:#202122;">Enzymklassifikation

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<td><a href="EC-Nummer" title="EC-Nummer">EC, Kategorie</a>

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<td colspan="2" class="" style="text-align:center;"><a rel="nofollow" class="external text" href="https://www.brenda-enzymes.org/enzyme.php?ecno=1.2.4.1">1.2.4.1</a>, <a href="Oxidoreduktase" class="mw-redirect" title="Oxidoreduktase">Oxidoreduktase</a>

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<td>Substrat

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<td colspan="2" style="text-align:center;">Pyruvat + Lipoyllysin-PDHE2

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<td>Produkte

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<td colspan="2" style="text-align:center;">S-Acetyldihydrolipoyllysin -PDHE2 + CO<sub>2</sub>

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<th colspan="3" style="background:#90EE90; color:#202122;">Vorkommen

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<td style="background:#C3FDB8; color:#202122;">Übergeordnetes <a href="Taxon" title="Taxon">Taxon</a>

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<td colspan="2" style="text-align:center;">Lebewesen

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</p><p><b>Pyruvatdehydrogenase E1</b> (<b>PDHE1</b>) ist der Name für die Untereinheit E1 des <a href="Pyruvatdehydrogenase-Komplex" title="Pyruvatdehydrogenase-Komplex">Pyruvatdehydrogenase-Enzymkomplexes</a>. PDHE1 <a href="Katalyse" title="Katalyse">katalysiert</a> die Übertragung eines <a href="Acetyl" class="mw-redirect" title="Acetyl">Acetylrests</a> auf das an die Untereinheit <a href="Dihydrolipoyl-Transacetylase" title="Dihydrolipoyl-Transacetylase">E2</a> gebundene Lipoyllysin, wobei ein Molekül <a href="Kohlenstoffdioxid" title="Kohlenstoffdioxid">Kohlenstoffdioxid</a> frei wird. E1 selbst besteht aus zwei α- und zwei β-Untereinheiten. Von α gibt es beim Menschen eine zweite Isoform, die speziell in den Hoden exprimiert wird.

</p><p><a href="Mutation" title="Mutation">Mutationen</a> in den <a href="Gen" title="Gen">Genen</a>, die für α und β <a href="Genetischer_Code" title="Genetischer Code">kodieren</a> (in α allein sind 80 bekannt), können <a href="Pyruvat-Dehydrogenase-Mangel" title="Pyruvat-Dehydrogenase-Mangel">PDHE1-Mangel</a> bis hin zum <a href="Leigh-Syndrom" title="Leigh-Syndrom">Leigh-Syndrom</a> und <a href="Laktatazidose" title="Laktatazidose">Laktatazidose</a> verursachen.<sup id="cite_ref-u_1-0" class="reference"><a href="#cite_note-u-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-3" class="reference"><a href="#cite_note-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup>

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<div class="mw-heading mw-heading2"><h2 id="Katalysierte_Reaktion">Katalysierte Reaktion</h2></div>

<p>Die <a href="Decarboxylierung" title="Decarboxylierung">Decarboxylierung</a> von Pyruvat findet am Thiamin als katalytischem Zentrum statt, welches eine Atombindung mit Pyruvat bildet, so dass <a href="Hydroxygruppe" title="Hydroxygruppe">Hydroxy</a>-Ethyliden-<a href="Thiamin" title="Thiamin">Thiamin</a>-<a href="Pyrophosphat" class="mw-redirect" title="Pyrophosphat">Pyrophosphat</a> unter Abspaltung von CO<sub>2</sub> entsteht.

</p><p><span typeof="mw:File"></span> + <span typeof="mw:File"></span> → <span typeof="mw:File"></span> →

<span typeof="mw:File"></span> + CO<sub>2</sub> (R=CH<sub>3</sub>)

</p><p>Dieser Hydroxy-Ethyliden-Rest (syn. <a href="Acetaldehyd" title="Acetaldehyd">Acetaldehyd</a>) des TPP wird von der <a href="Lipons%C3%A4ure" title="Liponsäure">α-Liponsäure</a> übernommen (<a href="Oxidation" title="Oxidation">Oxidation</a>). Sie ist an die <a href="Acetyltransferase" title="Acetyltransferase">Lipoat-Trans-Acetylase</a>-Untereinheit kovalent gebunden. Es entsteht S-Acetyl-Hydrolip(oat/onamid).

</p><p><span typeof="mw:File"></span> + <span typeof="mw:File"></span> → <span typeof="mw:File"></span> + <span typeof="mw:File"></span> (R=CH<sub>3</sub>)

</p><p>Es scheint, dass die zwei Thiamin-Moleküle im Tetramer nicht gleichzeitig die genannte Reaktionssequenz durchlaufen. In einer Kristallstudie wurde eine damit zusammenhängende Bewegung des Tetramers festgestellt.<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup>

</p><p>Die hodenspezifische Isoform des Enzyms spielt nach einer Studie an Hamstern eine Rolle bei der <a href="Kapazitation" title="Kapazitation">Kapazitation</a>.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup>

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<div class="mw-heading mw-heading2"><h2 id="Regulation">Regulation</h2></div>

<p>PDHE1 wird durch <a href="Phosphorylierung" title="Phosphorylierung">Phosphorylierung</a> der α-Einheit inaktiviert bzw. durch Dephosphorylierung aktiviert. Das entsprechende Enzym ist die PDH-Kinase (<a href="EC-Nummer" title="EC-Nummer">EC</a> <a rel="nofollow" class="external text" href="https://enzyme.expasy.org/EC/2.7.11.2">2.7.11.2</a>), welches selbst ein Teil der PDH ist (= Autophosphorylierung). Erhöhte Aktivität kann bereits durch erhöhte Muskelarbeit ausgelöst werden, wobei eine Abhängigkeit der PDH-Phosphatase von der mitochondrialen Ca<sup>2+</sup>-Konzentration diskutiert wird.<sup id="cite_ref-6" class="reference"><a href="#cite_note-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> Eine Hemmung durch <a href="Sepsis" title="Sepsis">Sepsis</a> konnte bei Ratten gezeigt werden.<sup id="cite_ref-u_1-1" class="reference"><a href="#cite_note-u-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup>

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<div class="mw-heading mw-heading2"><h2 id="Einzelnachweise">Einzelnachweise</h2></div>

<li id="cite_note-u-1"><span class="mw-cite-backlink">↑ <sup><a href="#cite_ref-u_1-0">a</a></sup> <sup><a href="#cite_ref-u_1-1">b</a></sup></span> <span class="reference-text"><a href="UniProt" title="UniProt">UniProt</a> <a rel="nofollow" class="external text" href="https://www.uniprot.org/uniprotkb/P08559">P08559</a></span>

</li>

<li id="cite_note-2"><span class="mw-cite-backlink"><a href="#cite_ref-2">↑</a></span> <span class="reference-text">Cameron JM, Levandovskiy V, Mackay N, Tein I, Robinson BH: <cite style="font-style:italic">Deficiency of pyruvate dehydrogenase caused by novel and known mutations in the E1alpha subunit</cite>. In: <cite style="font-style:italic">Am. J. Med. Genet. A</cite>. 131. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em"> </span>1</span>, November 2004, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em"> </span>59–66</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1002/ajmg.a.30287">10.1002/ajmg.a.30287</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/15384102?dopt=Abstract">PMID 15384102</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rfr_id=info:sid/de.wikipedia.org:Pyruvatdehydrogenase+E1&rft.atitle=Deficiency+of+pyruvate+dehydrogenase+caused+by+novel+and+known+mutations+in+the+E1alpha+subunit&rft.au=Cameron+JM%2C+Levandovskiy+V%2C+Mackay+N%2C+...&rft.date=2004-11&rft.doi=10.1002%2Fajmg.a.30287&rft.genre=journal&rft.issue=1&rft.jtitle=Am.+J.+Med.+Genet.+A&rft.pages=59-66&rft.pmid=15384102&rft.volume=131.+Jahrgang" style="display:none"> </span></span>

</li>

<li id="cite_note-3"><span class="mw-cite-backlink"><a href="#cite_ref-3">↑</a></span> <span class="reference-text">Han Z, Gorbatyuk M, Thomas J, Lewin AS, Srivastava A, Stacpoole PW: <cite style="font-style:italic">Down-regulation of expression of rat pyruvate dehydrogenase E1alpha gene by self-complementary adeno-associated virus-mediated small interfering RNA delivery</cite>. In: <cite style="font-style:italic">Mitochondrion</cite>. 7. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em"> </span>4</span>, Juli 2007, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em"> </span>253–9</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1016/j.mito.2007.02.003">10.1016/j.mito.2007.02.003</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/17392036?dopt=Abstract">PMID 17392036</a>, <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1973157/">PMC 1973157</a> (freier Volltext).<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rfr_id=info:sid/de.wikipedia.org:Pyruvatdehydrogenase+E1&rft.atitle=Down-regulation+of+expression+of+rat+pyruvate+dehydrogenase+E1alpha+gene+by+self-complementary+adeno-associated+virus-mediated+small+interfering+RNA+delivery&rft.au=Han+Z%2C+Gorbatyuk+M%2C+Thomas+J%2C+...&rft.date=2007-07&rft.doi=10.1016%2Fj.mito.2007.02.003&rft.genre=journal&rft.issue=4&rft.jtitle=Mitochondrion&rft.pages=253-9&rft.pmc=1973157&rft.pmid=17392036&rft.volume=7.+Jahrgang" style="display:none"> </span></span>

</li>

<li id="cite_note-4"><span class="mw-cite-backlink"><a href="#cite_ref-4">↑</a></span> <span class="reference-text">Ciszak EM, Korotchkina LG, Dominiak PM, Sidhu S, Patel MS: <cite style="font-style:italic">Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase</cite>. In: <cite style="font-style:italic">J. Biol. Chem.</cite> 278. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em"> </span>23</span>, Juni 2003, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em"> </span>21240–6</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1074/jbc.M300339200">10.1074/jbc.M300339200</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/12651851?dopt=Abstract">PMID 12651851</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rfr_id=info:sid/de.wikipedia.org:Pyruvatdehydrogenase+E1&rft.atitle=Structural+basis+for+flip-flop+action+of+thiamin+pyrophosphate-dependent+enzymes+revealed+by+human+pyruvate+dehydrogenase&rft.au=Ciszak+EM%2C+Korotchkina+LG%2C+Dominiak+PM%2C+...&rft.date=2003-06&rft.doi=10.1074%2Fjbc.M300339200&rft.genre=journal&rft.issue=23&rft.jtitle=J.+Biol.+Chem.&rft.pages=21240-6&rft.pmid=12651851&rft.volume=278.+Jahrgang" style="display:none"> </span></span>

</li>

<li id="cite_note-5"><span class="mw-cite-backlink"><a href="#cite_ref-5">↑</a></span> <span class="reference-text">Kumar V, Rangaraj N, Shivaji S: <cite style="font-style:italic">Activity of pyruvate dehydrogenase A (PDHA) in hamster spermatozoa correlates positively with hyperactivation and is associated with sperm capacitation</cite>. In: <cite style="font-style:italic">Biol. Reprod.</cite> 75. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em"> </span>5</span>, November 2006, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em"> </span>767–77</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1095/biolreprod.106.053587">10.1095/biolreprod.106.053587</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/16855207?dopt=Abstract">PMID 16855207</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rfr_id=info:sid/de.wikipedia.org:Pyruvatdehydrogenase+E1&rft.atitle=Activity+of+pyruvate+dehydrogenase+A+%28PDHA%29+in+hamster+spermatozoa+correlates+positively+with+hyperactivation+and+is+associated+with+sperm+capacitation&rft.au=Kumar+V%2C+Rangaraj+N%2C+Shivaji+S&rft.date=2006-11&rft.doi=10.1095%2Fbiolreprod.106.053587&rft.genre=journal&rft.issue=5&rft.jtitle=Biol.+Reprod.&rft.pages=767-77&rft.pmid=16855207&rft.volume=75.+Jahrgang" style="display:none"> </span></span>

</li>

<li id="cite_note-6"><span class="mw-cite-backlink"><a href="#cite_ref-6">↑</a></span> <span class="reference-text">Rassow J et al. 2008. Biochemie. 2. Auflage, Stuttgart: Thieme Verlag, 109.</span>

</li>

<li id="cite_note-7"><span class="mw-cite-backlink"><a href="#cite_ref-7">↑</a></span> <span class="reference-text">Stellingwerff T, Watt MJ, Heigenhauser GJ, Spriet LL: <cite style="font-style:italic">Effects of reduced free fatty acid availability on skeletal muscle PDH activation during aerobic exercise. Pyruvate dehydrogenase</cite>. In: <cite style="font-style:italic">Am. J. Physiol. Endocrinol. Metab.</cite> 284. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em"> </span>3</span>, März 2003, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em"> </span>E589–96</span>, <a href="Digital_Object_Identifier" title="Digital Object Identifier">doi</a>:<span class="uri-handle" style="white-space:nowrap"><a rel="nofollow" class="external text" href="https://doi.org/10.1152/ajpendo.00418.2002">10.1152/ajpendo.00418.2002</a></span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/12556353?dopt=Abstract">PMID 12556353</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rfr_id=info:sid/de.wikipedia.org:Pyruvatdehydrogenase+E1&rft.atitle=Effects+of+reduced+free+fatty+acid+availability+on+skeletal+muscle+PDH+activation+during+aerobic+exercise.+Pyruvate+dehydrogenase&rft.au=Stellingwerff+T%2C+Watt+MJ%2C+Heigenhauser+GJ%2C+...&rft.date=2003-03&rft.doi=10.1152%2Fajpendo.00418.2002&rft.genre=journal&rft.issue=3&rft.jtitle=Am.+J.+Physiol.+Endocrinol.+Metab.&rft.pages=E589-96&rft.pmid=12556353&rft.volume=284.+Jahrgang" style="display:none"> </span></span>

</li>

<li id="cite_note-8"><span class="mw-cite-backlink"><a href="#cite_ref-8">↑</a></span> <span class="reference-text">Vary TC: <cite style="font-style:italic">Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate</cite>. In: <cite style="font-style:italic">Shock</cite>. 6. Jahrgang, <span style="white-space:nowrap">Nr.<span style="display:inline-block;width:.2em"> </span>2</span>, August 1996, <span style="white-space:nowrap">S.<span style="display:inline-block;width:.2em"> </span>89–94</span>, <a class="external mw-magiclink-pmid" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pubmed/8856841?dopt=Abstract">PMID 8856841</a>.<span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rfr_id=info:sid/de.wikipedia.org:Pyruvatdehydrogenase+E1&rft.atitle=Sepsis-induced+alterations+in+pyruvate+dehydrogenase+complex+activity+in+rat+skeletal+muscle%3A+effects+on+plasma+lactate&rft.au=Vary+TC&rft.date=1996-08&rft.genre=journal&rft.issue=2&rft.jtitle=Shock&rft.pages=89-94&rft.pmid=8856841&rft.volume=6.+Jahrgang" style="display:none"> </span></span>

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<div class="mw-heading mw-heading2"><h2 id="Weblinks">Weblinks</h2></div>

<div class="sisterproject" style="margin:0.1em 0 0 0;"><div class="noviewer" style="display:inline-block; line-height:10px; min-width:1.6em; text-align:center;" aria-hidden="true" role="presentation"><span class="mw-default-size" typeof="mw:File"><span title="Wikibooks"></span></span></div><b><a href="https://de.wikibooks.org/wiki/Biochemie_und_Pathobiochemie:_Pyruvat-Dehydrogenase" class="extiw external" title="b:Biochemie und Pathobiochemie: Pyruvat-Dehydrogenase">Wikibooks: Biochemie und Pathobiochemie: Pyruvat-Dehydrogenase</a></b> – Lern- und Lehrmaterialien</div></div><div><div class="zim-footer">

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