Pyruvate dehydrogenase: Difference between revisions

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The enzyme requires <scene name='Kenny_Coggins_Sandbox_1/Thdp/5'>TPP and Mg2+</scene> as cofactors for catalysis.  [[Image:Thiamine pyrophosphate.png|thumb|left|alt=Thiamine pyrophosphate.|Thiamine pyrophosphate (TPP) E1 cofactor.]]  
The enzyme requires <scene name='Kenny_Coggins_Sandbox_1/Thdp/5'>TPP and Mg2+</scene> as cofactors for catalysis.  [[Image:Thiamine pyrophosphate.png|thumb|left|alt=Thiamine pyrophosphate.|Thiamine pyrophosphate (TPP) E1 cofactor.]]  
 
{{Clear}}
In this reaction, the ylide form of TPP attacks the electrophilic carbonyl group of pyruvate.  This reflects the ability of TPP’s thiazolium ring, which primarily interacts with <scene name='Kenny_Coggins_Sandbox_1/Ile569_asp521/5'>Ile569 and Asp521</scene>, to add to carbonyl groups.  Decarboxylation of the resulting alkoxide yields an enol complex.  This enol resonates to form the ylide form of hydroxyethyl-TPP<ref name="book">Voet, D., Voet, J.G., and Pratt, C.W.  (2008). Fundamentals of biochemistry. Hoboken, NJ: John Wiley and Sons, Inc.</ref>.  During this reaction, the catalytic Mg2+ ion coordinates octahedrally with three protein ligands: <scene name='Kenny_Coggins_Sandbox_1/Asp230_and_asn260/2'>Asp230 and Asn 260</scene>, which bind TPP, and <scene name='Kenny_Coggins_Sandbox_1/Glu262/2'>Glu262</scene><ref name="PMID" />.  
In this reaction, the ylide form of TPP attacks the electrophilic carbonyl group of pyruvate.  This reflects the ability of TPP’s thiazolium ring, which primarily interacts with <scene name='Kenny_Coggins_Sandbox_1/Ile569_asp521/5'>Ile569 and Asp521</scene>, to add to carbonyl groups.  Decarboxylation of the resulting alkoxide yields an enol complex.  This enol resonates to form the ylide form of hydroxyethyl-TPP<ref name="book">Voet, D., Voet, J.G., and Pratt, C.W.  (2008). Fundamentals of biochemistry. Hoboken, NJ: John Wiley and Sons, Inc.</ref>.  During this reaction, the catalytic Mg2+ ion coordinates octahedrally with three protein ligands: <scene name='Kenny_Coggins_Sandbox_1/Asp230_and_asn260/2'>Asp230 and Asn 260</scene>, which bind TPP, and <scene name='Kenny_Coggins_Sandbox_1/Glu262/2'>Glu262</scene><ref name="PMID" />.  


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The overall mechanism is shown as following:
The overall mechanism is shown as following:


[[Image:PyruvateDehydrgenaseMech.gif|left|500px]]
[[Image:PyruvateDehydrgenaseMech.gif]]


==Regulation==
==Regulation==