In the HMP shunt (pentose phosphate pathway), glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme. Which metabolite serves as both the allosteric activator of glucose-6-phosphate dehydrogenase and the immediate oxidising cosubstrate?

• A NADH — produced in equal amounts to NADPH
• B Glucose-6-phosphate — direct substrate that also activates the enzyme
• C Ribulose-5-phosphate — feedback activator of G6PD
• D NADP+ — its ratio relative to NADPH determines G6PD activity ✓

Explanation

G6PD is allosterically regulated by the NADP+/NADPH ratio: high NADP+ (low NADPH) — indicating oxidative stress — activates G6PD, increasing flux through the HMP shunt to regenerate NADPH. NADP+ is also the direct cosubstrate oxidised to NADPH in the first irreversible step (glucose-6-phosphate → 6-phosphogluconolactone). When NADPH is abundant (high NADPH, low NADP+), G6PD is inhibited by product inhibition. In G6PD deficiency, inadequate NADPH production impairs glutathione reductase, depleting reduced glutathione (GSH) in red cells and causing haemolysis under oxidative stress.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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