Oxidation of Pyruvate to Acetyl-CoA

In this article we will discuss about the Oxidation of Pyruvate to Acetyl-CoA.

1. Pyruvate oxidatively decarboxylated to acetyl-CoA (“active acetate”) before en­tering the citric acid cycle.

2. The reaction is catalysed by the multi-enzyme complex consisting of sev­eral different enzymes. This complex is known as pyruvate dehydrogenase com­plex.

3. Pyruvate is decarboxylated in the pres­ence of thiamine pyrophosphate (TPP) to a hydroxymethyl derivative which reacts with oxidized lipoate to from S-acetyl lipoate being catalyzed by the enzyme pyruvate dehydrogenase.

4. S-acetyl lipoate reacts with coenzyme A to form acetyl-CoA and reduced lipoate in presence of di-hydrolipoyl transacetylase.

5. The reduced lipoate is re-oxidized by FAD in presence of dihydrolipoyl dehydroge­nase.

6. Finally, the reduced FAD is oxidized by NAD⁺. The reduced NAD (NADH + H⁺) enters the respiratory chain producing 3 ATP.

7. The pyruvate dehydrogenase complex consists of about 29 mols of pyruvate de­hydrogenase and 8 mols of dihydorlipoyl dehydrogenase distributed around 1 mol of transacetylase.

Regulation:

1. The increased pyruvic acid from carbohy­drate diet inhibits pyruvate dehydrogenase kinase for which active pyruvate de­hydrogenase is formed. This causes the rapid breakdown of pyruvic acid to form acetyl-CoA.

2. Actyl-CoA and NADH formed by en­hanced p-oxidation during starvation and diabetes mcllitus activate pyruvate dehy­drogenase kinase decreasing the “active” form of pyruvate dehydrogenase. Hence, less pyruvic acid is catabolized and gly­colysis is also inhibited.

Inhibitors:

Arsenitc inhibits pyruvate dehydrogenase and dietary deficiency of thiamine also allows pyru­vate to accumulate. Chronic alcoholics also suffer from the defi­ciency of thiamine which results in the accumulation of pyruvic acid. Lactic acidosis is caused by the inherited deficiency of pyruvate dehydroge­nase.