Question

Pyruvate dehydrogenase is an important point in the regulation of the transition between glycolysis and the TCA cycle. What reaction does his enzyme catalyze? Show the molecular structures of the reactants and products, and any other molecules that participate. Show all the ways that key enzyme regulated- allosteric activators, inhibitors, and more.

Answer 1

Pyruvate dehydrogenase : It is multiple enzyme complex. It consists of 3 enzymatic subunits and 5 coenzymes.

The three enzymatic subunits are :

a) E1 : Pyruvate dehydrogenase or pyruvate decarboxylase

b) E2 : Dihydrolipoyl transacetylase

c) E3 : Dihydrolipoyl dehydrogenase

The five coenzymes are :

1) Thiamine pyrophosphate (TPP), 2) Lipoid acid 3) Flavin adenine dinucleotide (FAD) 4) Coenzyme A and 5) Nicotinamide adenine dinucleotide (NAD)

It mainly involves in the conversion of pyruvate to acetyl coenzyme A through 5 steps :

Step 1: Decarboxylation of pyruvate takes place and reacts with TPP to form hydroxyl methyl derivative of thiazole ring of TPP.

Step 2 : The hydrogen and acetyl groups are transferred to the oxidised form of lipoyl group of enzyme E2 and form 6-acetyl thioester of the reduced lipoyl groups

Step 3 : Coenzyme A reacts with acetyl derivative of enzyme E2 to produce acetyl coA and reduces lipoyl group.

Step 4 : Transfer of hydrogen atom from lipoyl group of E2 to the FAD prosthetic group of E3 takes place

Step 5 : The reduced group of E3 transfer hydrogen to NAD⁺ and form NADH

The regulators of pyruvate dehydrogenase are given in the below image :

Pyruvate dehydrogenase (PDH) complex is regulated usually by the allosteric and covalent modifications by the action of enzymes like pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase.

These enzymes are again regulated by the other substrates like acetyl coA, [ATP/[ADP], NADH. pyruvate, insulin etc

The allosteric inhibitors of PDH complex are NADH and acetyl coenzyme A which are end products of reaction.