Q.17 What is the significance of the isomerization of glucose 6–phosphate to fructose 6–phosphate for the
progression of glycolysis?
(A) As functional groups, ketones are more reactive than aldehydes
(B) Cleavage of glucose 1,6–bisphosphate will not yield dihydroxy acetone phosphate and
glyceraldehyde 3–phosphate
(C) The carbonyl group at carbon–2 (C–2) in fructose facilitates the cleavage of the bond between
C–3 and C–4
(D) Phosphorylation of glucose 6–phosphate to glucose 1,6–bisphosphate is irreversible

The correct answer is (C).

The isomerization of glucose 6-phosphate to fructose 6-phosphate, catalyzed by phosphoglucose isomerase, is a key step in glycolysis that positions the carbonyl group at C-2. This structural change enables the subsequent aldolase enzyme to efficiently cleave fructose 1,6-bisphosphate between C-3 and C-4 into two triose phosphates: dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.​

Option Analysis

(A) Ketones more reactive than aldehydes

Ketones are generally less reactive than aldehydes toward nucleophiles due to steric hindrance and lower electrophilicity. This does not explain the need for isomerization in glycolysis, as the reaction relies on carbonyl positioning rather than inherent reactivity differences.​

(B) Cleavage of glucose 1,6-bisphosphate issue

Glycolysis forms fructose 1,6-bisphosphate, not glucose 1,6-bisphosphate, after phosphofructokinase acts on fructose 6-phosphate. Cleavage occurs symmetrically only with the ketose form at C-2.​

(C) C-2 carbonyl facilitates C-3/C-4 cleavage (Correct)

The C-2 carbonyl in fructose 1,6-bisphosphate acts as an electron sink, stabilizing the retro-aldol cleavage between C-3 and C-4 by accepting electrons from the breaking bond. An aldose carbonyl at C-1 (as in glucose) cannot perform this role effectively.​

(D) Phosphorylation of glucose 6-phosphate irreversible

No such direct phosphorylation to glucose 1,6-bisphosphate occurs in glycolysis; the pathway uses fructose 6-phosphate for the second phosphorylation. The initial glucose to glucose 6-phosphate step is reversible, but this is unrelated.​

The isomerization of glucose 6-phosphate to fructose 6-phosphate represents a pivotal step in glycolysis, enabling efficient carbon chain cleavage for energy production. This reaction, driven by phosphoglucose isomerase, converts an aldose to a ketose, setting the stage for symmetrical splitting into triose phosphates.​

Glycolysis Pathway Overview

Glycolysis breaks down glucose into pyruvate through 10 enzyme-catalyzed steps, investing 2 ATP initially for a net gain of 2 ATP and 2 NADH.​

• Step 1: Hexokinase phosphorylates glucose to glucose 6-phosphate.

• Step 2: Isomerization occurs here, shifting the carbonyl from C-1 to C-2.​

• Step 5: Aldolase cleaves fructose 1,6-bisphosphate at C-3/C-4.​

Biochemical Mechanism

During isomerization, the enzyme opens the glucose ring, forms an enediol intermediate, and reforms as fructose 6-phosphate. The C-2 ketone in the subsequent bisphosphate stabilizes the carbanion intermediate in aldolase’s retro-aldol reaction, unlike a C-1 aldehyde which would yield asymmetric products.​

Exam Relevance for CSIR NET

This concept tests understanding of glycolytic logic and enzyme specificity, often appearing in MCQs on metabolic pathways. Recognizing the electron-withdrawing role of the C-2 carbonyl distinguishes correct options in questions.​