Which enzyme catalyzes the rate-limiting step of the oxidative phase of the pentose phosphate pathway?

Question

Accepted Answer

C. Glucose-6-phosphate dehydrogenase. ## Oxidative Phase of the Pentose Phosphate Pathway

**Key Point:** Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the first and rate-limiting step of the oxidative phase, converting glucose-6-phosphate to 6-phosphogluconolactone while reducing NADP^+^ to NADPH.

**High-Yield:** This is the committed step of the pathway. The reaction is irreversible and highly regulated by the availability of NADP^+^ and the concentration of NADPH (product inhibition).

### Why G6PD is Rate-Limiting

| Feature | Details |
| --- | --- |
| **Enzyme** | Glucose-6-phosphate dehydrogenase (G6PD) |
| **Substrate** | Glucose-6-phosphate |
| **Product** | 6-Phosphogluconolactone + NADPH |
| **Cofactor** | NADP^+^ (essential) |
| **Regulation** | Inhibited by high NADPH/NADP^+^ ratio |
| **Clinical Significance** | Deficiency causes hemolytic anemia (G6PD deficiency) |

**Mnemonic:** **G6PD** = **G**lucose-**6**-**P**hosphate **D**ehydrogenase — the gatekeeper of the oxidative pentose phosphate pathway.

**Clinical Pearl:** G6PD deficiency is the most common enzyme deficiency worldwide, affecting ~400 million people. Hemolysis is triggered by oxidative stress (fava beans, sulfonamides, antimalarials like primaquine).

### Other Enzymes in the Pathway

- **6-Phosphogluconate dehydrogenase**: Second oxidative enzyme; also produces NADPH but is not rate-limiting.
- **Phosphoglucose isomerase**: Glycolytic enzyme; not part of the pentose phosphate pathway.
- **Glucose-6-phosphatase**: Gluconeogenic enzyme; found in liver and kidney, not in the pentose phosphate pathway.

![Pentose Phosphate Pathway diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/4054.webp)

Answer

A. Glucose-6-phosphatase

Answer

B. Phosphoglucose isomerase

Answer

D. 6-Phosphogluconate dehydrogenase

Feature	Details
Enzyme	Glucose-6-phosphate dehydrogenase (G6PD)
Substrate	Glucose-6-phosphate
Product	6-Phosphogluconolactone + NADPH
Cofactor	NADP⁺ (essential)
Regulation	Inhibited by high NADPH/NADP⁺ ratio
Clinical Significance	Deficiency causes hemolytic anemia (G6PD deficiency)

Which enzyme catalyzes the rate-limiting step of the oxidative phase of the pentose phosphate pathway?

Explanation

Oxidative Phase of the Pentose Phosphate Pathway

Why G6PD is Rate-Limiting

Other Enzymes in the Pathway

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