Which enzyme catalyzes the conversion of succinyl-CoA to succinate in the TCA cycle, and what is its cofactor requirement?

Question

Accepted Answer

C. Succinyl-CoA synthetase; requires GTP/ATP and CoA. ## TCA Cycle: Succinyl-CoA to Succinate Conversion

### Enzyme Identity
**Key Point:** Succinyl-CoA synthetase (also called succinate thiokinase) catalyzes the only substrate-level phosphorylation step in the TCA cycle.

### Cofactor and Reaction
**High-Yield:** The reaction requires:
- **Cofactor:** GTP (or ATP in some tissues, particularly liver)
- **Substrate:** CoA
- **Product:** Succinate + GTP/ATP (energy capture)

### Mechanism
The enzyme cleaves the high-energy thioester bond of succinyl-CoA and couples the energy release to GTP/ATP synthesis. This is the only direct ATP/GTP-generating step in the cycle; all other ATP comes from the electron transport chain.

### Clinical Significance
**Clinical Pearl:** Deficiency of succinyl-CoA synthetase is rare but causes mitochondrial encephalomyopathy with accumulation of succinyl-CoA and succinylcarnitine in urine.

### Comparison with Other TCA Enzymes

| Enzyme | Substrate | Product | Cofactor | Energy Yield |
|--------|-----------|---------|----------|---------------|
| Succinyl-CoA synthetase | Succinyl-CoA | Succinate | GTP/ATP, CoA | GTP/ATP (substrate-level) |
| Succinate dehydrogenase | Succinate | Fumarate | FAD | FADH₂ (oxidative) |
| Isocitrate dehydrogenase | Isocitrate | α-ketoglutarate | NAD⁺ | NADH (oxidative) |
| Fumarase | Fumarate | Malate | — | None (hydration) |

**Mnemonic:** **"SUCKED IN"** — Succinyl-CoA synthetase Uses CoA, Kinase Energy, Drives nucleotide (GTP/ATP) synthesis.

![TCA Cycle diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/3490.webp)

Answer

A. Isocitrate dehydrogenase; requires NAD+

Answer

B. Fumarase; requires water

Answer

D. Succinate dehydrogenase; requires FAD

Which enzyme catalyzes the conversion of succinyl-CoA to succinate in the TCA cycle, and what is its cofactor requirement?

Explanation

TCA Cycle: Succinyl-CoA to Succinate Conversion

Enzyme Identity

Cofactor and Reaction

Mechanism

Clinical Significance

Comparison with Other TCA Enzymes

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Enzyme	Substrate	Product	Cofactor	Energy Yield
Succinyl-CoA synthetase	Succinyl-CoA	Succinate	GTP/ATP, CoA	GTP/ATP (substrate-level)
Succinate dehydrogenase	Succinate	Fumarate	FAD	FADH₂ (oxidative)
Isocitrate dehydrogenase	Isocitrate	α-ketoglutarate	NAD⁺	NADH (oxidative)
Fumarase	Fumarate	Malate	—	None (hydration)