Q. 40 Which one the following reaction mechanisms drives the conversion of low energy
3phosphoglyceraldehyde to high energy 1,3-bisphosphoglycerate?
(A) Oxidation without anhydride bond formation
(B) Oxidation coupled with anhydride bond formation
(C) Substrate level phosphorylation
(D) Formation of carboxylate

The conversion of low-energy 3-phosphoglyceraldehyde (also known as glyceraldehyde-3-phosphate or G3P) to high-energy 1,3-bisphosphoglycerate (1,3-BPG) occurs in glycolysis step 6, catalyzed by glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This reaction involves oxidation of G3P’s aldehyde group and simultaneous formation of a high-energy acyl phosphate bond, making option (B) Oxidation coupled with anhydride bond formation the correct answer.

Reaction Overview

G3P binds to GAPDH’s active site cysteine, forming a thiohemiacetal intermediate that oxidizes to a thioester, reducing NAD+ to NADH. Inorganic phosphate then displaces the thioester, creating 1,3-BPG’s high-energy mixed anhydride (acyl phosphate) bond without ATP input. This couples oxidation energy to phosphorylation, storing it for later ATP production via phosphoglycerate kinase.

Correct Answer: Option (B)

Oxidation coupled with anhydride bond formation precisely describes the mechanism. The aldehyde oxidizes while phosphate adds, forming the anhydride-like C-O-P bond in 1,3-BPG, which has a ΔG°’ of -49 kJ/mol hydrolysis energy.

Option Explanations

• (A) Oxidation without anhydride bond formation: Incorrect, as oxidation directly forms the high-energy acyl phosphate anhydride bond; no uncoupled oxidation occurs.

• (B) Oxidation coupled with anhydride bond formation: Correct, per the enzyme mechanism linking NADH production to phosphate addition.

• (C) Substrate level phosphorylation: Incorrect here; this describes the next step (1,3-BPG to 3-PG + ATP). Step 6 uses inorganic phosphate, not substrate-level ATP transfer.

• (D) Formation of carboxylate: Incorrect; while a carboxylic acid intermediate forms transiently, the product retains the high-energy phosphate, not a free carboxylate.