2 - Pyruvate Dehydrogenase Complex

What is the molecular mass of the Pyruvate Dehydrogenase Complex?

Over 1,000,000 g/mole

What are the four types of subunits in the Pyruvate Dehydrogenase Complex?

• E1 – Pyruvate Dehydrogenase

• E2 – Dihydrolipoyl Transacetylase

• E3 – Dihydrolipoyl Dehydrogenase

• Kinase/Phosphatase – regulatory subunit (same polypeptide)

What are the approximate subunit counts in mammals for each component of the PDC?

E1: 20–30 copies

E2: ~60 copies

E3: 20–30 copies

Kinase/Phosphatase: variable; increases with starvation

What are the two cosubstrates required for PDC activity?

• NAD⁺

• Coenzyme A (CoA-SH)

What three coenzymes are required by the Pyruvate Dehydrogenase Complex?

Thiamine Pyrophosphate (TPP)

Lipoic Acid

Flavin Adenine Dinucleotide (FAD)

Which vitamins are the coenzymes and cosubstrates derived from?

Thiamine → TPP

Pantothenic acid → Coenzyme A

Niacin → NAD⁺

Riboflavin → FAD

What is the overall reaction catalyzed by the PDC?

Pyruvate + CoA + NAD⁺ → Acetyl-CoA + CO₂ + NADH

What type of cleavage occurs in the first step of the PDC reaction?

An α-cleavage (decarboxylation) of pyruvate catalyzed by E1 using TPP

What role does E2 (Dihydrolipoyl Transacetylase) play in the PDC reaction?

Transfers the acetyl group to lipoic acid, then to CoA, forming acetyl-CoA

What role does E3 (Dihydrolipoyl Dehydrogenase) play in the PDC reaction?

Reoxidizes reduced lipoic acid and transfers electrons to FAD → FADH₂, then to NAD⁺ → NADH