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.]] | ||
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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 | [[Image:PyruvateDehydrgenaseMech.gif]] | ||
==Regulation== | ==Regulation== | ||