Which enzyme catalyzes the first committed step of the pentose phosphate pathway and is inhibited by its product NADPH?

Explanation

## Pentose Phosphate Pathway — Oxidative Phase **Key Point:** Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first and rate-limiting step of the pentose phosphate pathway, converting glucose-6-phosphate to 6-phosphogluconolactone while generating NADPH. ### Enzyme Characteristics | Feature | G6PD | | --- | --- | | Substrate | Glucose-6-phosphate | | Product | 6-phosphogluconolactone + NADPH | | Cofactor | NADP^+^ | | Regulation | Inhibited by NADPH (product inhibition) | | Location | Cytoplasm | | Genetic defect | X-linked (G6PD deficiency) | **High-Yield:** NADPH is a powerful allosteric inhibitor of G6PD. When the cell has sufficient reducing power, the enzyme is shut down — this is the primary regulatory mechanism of the pathway. **Clinical Pearl:** G6PD deficiency is the most common enzyme defect worldwide, affecting ~400 million people. Patients develop hemolytic anemia when exposed to oxidative stress (fava beans, sulfonamides, aspirin). **Mnemonic:** **G6PD = Gateway enzyme** — it is the committed first step; once glucose-6-phosphate enters the PPP, it is committed to NADPH production rather than glycolysis. ### Why This Pathway Matters - Generates NADPH for biosynthetic reductions (fatty acid synthesis, cholesterol synthesis, glutathione reduction) - Produces ribose-5-phosphate for nucleotide synthesis - Provides antioxidant defense via NADPH-dependent glutathione reduction