Which enzyme catalyzes the conversion of pyruvate to acetyl-CoA?

• A. Pyruvate dehydrogenase complex (PDH).
• B. Pyruvate carboxylase.
• C. Citrate synthase.
• D. Lactate dehydrogenase.

Answer: (A)

Conversion of pyruvate to acetyl-CoA is carried out by the pyruvate dehydrogenase complex, a mitochondrial multi-enzyme assembly that sits at the gateway between glycolysis and the citric acid cycle. It performs oxidative decarboxylation of pyruvate: CO2 is released, the remaining two-carbon fragment is transferred to coenzyme A to form acetyl-CoA, and NAD+ is reduced to NADH. The complex works through a sequence where E1 decarboxylates pyruvate, transfers the acetyl group to the lipoamide arm of E2, which then passes it to CoA; E3 reoxidizes the lipoamide, transferring electrons to NAD+. This reaction tightly regulates flux into the TCA cycle and is controlled by cellular energy state: high NADH, high acetyl-CoA, or high ATP levels inhibit it, while activation occurs when energy is needed.

The other enzymes mentioned do different jobs: pyruvate carboxylase adds a carboxyl group to pyruvate to form oxaloacetate, not acetyl-CoA; citrate synthase condenses acetyl-CoA with oxaloacetate to form citrate in the TCA cycle; lactate dehydrogenase reduces pyruvate to lactate under anaerobic conditions.