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 **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.