Question:

Match List-I with List-II

List-I (Coenzyme/Prosthetic group of PDH) & List-II (Location on Multienzyme Complex)
(A) Nicotinamide adenine dinucleotide & (I) Bound to Dihydrolipoyl dehydrogenase (E3)
(B) Lipoic acid & (II) Covalently linked to a Lysine on E2
(C) Coenzyme A & (III) Substrate for E2
(D) Flavin adenine dinucleotide (FAD) & (IV) Substrate for E3

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The five coenzymes of the Pyruvate Dehydrogenase complex can be remembered using the mnemonic: Tender Loving Care For Nobody (Thiamine pyrophosphate (E1), Lipoic acid (E2), Coenzyme A (E2 substrate), FAD (E3), NAD (E3 substrate)).
  • (A) - (I), (B) - (II), (C) - (III), (D) - (IV)
  • (A) - (IV), (B) - (II), (C) - (III), (D) - (I)
  • (A) - (II), (B) - (III), (C) - (IV), (D) - (I)
  • (A) - (III), (B) - (IV), (C) - (I), (D) - (II)
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The Correct Option is B

Solution and Explanation

Step 1: Understanding the Concept:
The Pyruvate Dehydrogenase (PDH) complex is a large, highly organized multienzyme assembly that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA.
This complex is composed of multiple copies of three distinct enzymes: Pyruvate Dehydrogenase (E1), Dihydrolipoyl transacetylase (E2), and Dihydrolipoyl dehydrogenase (E3), which require five different coenzymes to function.

Step 2: Detailed Explanation:

Let us analyze the structural location and role of each coenzyme within the PDH complex:
1. Nicotinamide adenine dinucleotide (NAD${}^+$): This coenzyme serves as the terminal electron acceptor of the complex.
It binds transiently to the active site of E3 during the final step of the reaction cycle, where it is reduced to NADH by accepting electrons from FADH${}_2$.
Thus, it acts as a mobile substrate for E3. (A) matches with (IV).
2. Lipoic acid: This coenzyme serves as an electron and acyl carrier.
It is covalently linked via an amide bond to the $\epsilon$-amino group of a specific lysine residue on the E2 subunit (Dihydrolipoyl transacetylase), forming a flexible "lipoamide arm" that swings between active sites.
Thus, (B) matches with (II).
3. Coenzyme A (CoA-SH): This coenzyme serves as the acceptor for the acetyl group.
It acts as a substrate for the E2 subunit, where it receives the acetyl group from the acetyl-lipoamide intermediate to produce the final acetyl-CoA product.
Thus, it acts as a substrate for E2. (C) matches with (III).
4. Flavin adenine dinucleotide (FAD): This coenzyme serves as an intermediate electron carrier.
It is tightly bound as a prosthetic group to the E3 subunit (Dihydrolipoyl dehydrogenase), accepting electrons from the reduced lipoamide arm of E2.
Thus, (D) matches with (I).
Combining these matches, we get: (A) - (IV), (B) - (II), (C) - (III), (D) - (I).

Step 3: Final Answer:

The correct matching sequence is (A) - (IV), (B) - (II), (C) - (III), (D) - (I), which corresponds to option (B).
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