Step 1: Understanding the Concept:
The pyruvate dehydrogenase complex (PDC) is a multi-enzyme complex that links glycolysis to the citric acid cycle by catalyzing the oxidative decarboxylation of pyruvate to acetyl-CoA. The reaction proceeds in a specific sequence of steps involving three enzymes (E1, E2, E3) and five cofactors.
Step 2: Detailed Explanation:
The sequence of events is as follows:
(A) Decarboxylation of pyruvate: The enzyme pyruvate dehydrogenase (E1) removes a carboxyl group from pyruvate, releasing it as CO\(_2\). The remaining two-carbon fragment is attached to the thiamine pyrophosphate (TPP) cofactor.
(C) Formation of acetyl lipoamide: The two-carbon acetyl group is then transferred from TPP to the oxidized lipoamide arm of the second enzyme, dihydrolipoyl transacetylase (E2). This creates an acetyl-lipoamide intermediate.
(B) Formation of Acetyl-CoA: The acetyl group is transferred from the acetyl-lipoamide to coenzyme A, forming the final product, acetyl-CoA. The lipoamide arm is left in its reduced form (dihydrolipoamide).
(D) Oxidation of dihydrolipoamide: The third enzyme, dihydrolipoyl dehydrogenase (E3), re-oxidizes the dihydrolipoamide arm. The electrons are transferred first to FAD to make FADH\(_2\), and then to NAD\(^+\) to produce NADH, regenerating the complex for the next cycle.
Step 3: Final Answer:
The correct chronological order of the reactions is (A) \(\rightarrow\) (C) \(\rightarrow\) (B) \(\rightarrow\) (D). This matches option (2).