pyruvate decarboxylation

Meaning: Pyruvate from glycolysis enters the mitochondrial matrix, where the pyruvate dehydrogenase complex removes its carboxyl group as CO₂, oxidizes the remaining two-carbon unit, and attaches it to coenzyme A as acetyl-CoA. The electrons go to NAD⁺, forming NADH. Cofactors include thiamine pyrophosphate, lipoic acid, CoA, FAD and NAD⁺. The reaction is essentially irreversible, so animals cannot make net glucose from acetyl-CoA. High NADH and acetyl-CoA inhibit the complex, and phosphorylation by a kinase also inactivates it.

Equation: pyruvate + NAD⁺ + CoA-SH → acetyl-CoA + NADH + CO₂ (every species in mol; 1 mol of each per mol of pyruvate).

On the MCAT: Passages ask you to count products per glucose (2 acetyl-CoA, 2 NADH, 2 CO₂), to place the step in the matrix between glycolysis and the citric acid cycle, or to predict the effect of impairing the complex, for example by thiamine deficiency: pyruvate and lactate build up and less acetyl-CoA enters the cycle. Product inhibition by high NADH and acetyl-CoA is also tested.

Common confusion: This step is not part of the citric acid cycle, and it makes no ATP directly. It is also different from yeast fermentation, where pyruvate decarboxylase makes acetaldehyde and CO₂ without producing NADH.