Question

Pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl CoA. In this reaction, five cofactors (a) thiamine pyrophosphate; (b) nicotine adenine dinucleotide (NAD+); (c) acetylCoA; (d) flavin adenine dinucleotide (FAD); and (e) lipoamide participate at various steps of the reaction. Explain the role of each cofactor in this reaction. You must use the chemical structures and electronic properties of the intermediates to justify your answers.

Answer 1

Answer-

According to the given question-

We know that during Glycolysis one molecule of glucose produce two molecule of pyruvate which later oxidized into Acetyl CoA with the help of enzyme Pyruvate dehydrogenase complex and later this Acetyl Co A enters citric acid cycle and Electron transport chain.

Pyruvate Dehydrogenase Complex have three different enzymes such as pyruvate dehydrogenase or E1, dihydrolipoyl transacetylase or E2 and dihydrolipoyl dehydrogenase or E3.

Pyruvate Dehydrogenase Complex require five Coenzymes during oxidative decarboxylation step.which are thiamine pyrophosphate or TPP , lipoic acid, FAD , CoA and NAD+ .

In this reaction TPP , lipoic acid, and FAD work as catalytic cofactors while CoA and NAD+ as stoichiometric cofactors.

pyruvate is converted into acetyl CoA through three sequential steps such as- : decarboxylation followed by oxidation followed by acetyl group transfer CoA.

During this step pyruvate combines with thiamine pyrophosphate followed by decarboxylation occur with the help of pyruvate dehydrogenase or E1.

TPP form a carbanion,for addition of carbonyl group of pyruvate.

TPP has a positive charged ring which acts as an electron sink and helps in stabiliation of negative charge which are transferred during decarboxylation and this leads to formation of hydroxyethyl-TPP.
In next step the hydroxyethyl group which are attached to TPP is oxidizedand leads to formation of acetyl group and transferredthis group to lipoamide, which is a derivative of lipoic acid.

The disulfide group of lipoamide is reduced into disulfhydryl form with the help of pyruvate dehydrogenase to form acetyllipoamide.

After that the acetyl group from acetyllipoamide is transferred to CoA and leads to formation of acetyl CoA.

thioester bond which is energy-rich in acetyl group is transferred to CoA with the help of Dihydrolipoyl transacetylase or E2.

After that oxidation of dihydrolipoamide into lipoamide occur.Later this oxidized lipoamide is regenerated with the help of dihydrolipoyl dehydrogenase or E3.

here 2 electrons are transferred to FAD followed by then to NAD+.