Metabolism

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Oxidative decarboxylation

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Pyruvate's third fate is to generate acetyl-coA:

pyruvate+HS-CoA +NAD+ --> Acetyl CoA +CO2+NADH

This is known as the

The acetyl-coA formed is committed into entry to the

and can ultimately produce ATP via oxidative phosphorylation

The pyruvate dehydrogenase complex which allows the link reaction to occur is huge, it consists of 3 enzymes and 5 cofactors

3 enzymes are:

Pyruvate decarboxylase with a

prosthetic group

with a lipoamide prosthetic group

Dihydrolipoyl dehydrogenase with an

prosthetic group

The other two cofactors are NAD+ and

It starts with

trimers of lipoamide reductase-transacetylase

Then

dimers of dihydrolipoyl dehydrogenase

and 12 dimers of pyruvate decarboxylase

Thiamine pyrophosphate loses a proton readily and the resulting carbanion attacks that of pyruvate to yield hydroxyethyl-TPP

A deficiency of

is a cause of Beri-Beri whose symptoms include damage to the peripheral nervous system, weakness of the muscles and decreased cardiac output

FAD accepts and donates 2 electrons with

The pyruvate dehydrogenase complex: Decarboxylation of

to give hydroxyethyl-TPP, oxidation and transfer of

group to lipoamide to give acetylipoamide

Transfer of acetyl group to coA to give acetyl-coA, leaving reduced lipoamide.

Regeneration of oxidised lipoamide by FAD generating FADH2, regeneration of FAD by NAD+



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