Q.66 In TCA cycle, succinyl CoA synthetase is involved in the conversion of:
- α-ketoglutaric acid to succinyl CoA
- Succinic acid to fumaric acid
- Succinyl CoA to succinic acid
- Succinic acid to α-ketoglutaric acid
Succinyl CoA synthetase catalyzes Succinyl CoA → Succinic acid in the TCA cycle.
This enzyme performs substrate-level phosphorylation, converting succinyl CoA + GDP + Pi to succinate + GTP + CoA in step 5, generating high-energy GTP directly.
Option Analysis
α-ketoglutaric acid to succinyl CoA
α-ketoglutarate dehydrogenase complex (E1-E3) catalyzes oxidative decarboxylation: α-KG + NAD+ + CoA → succinyl CoA + CO2 + NADH. Succinyl CoA synthetase acts downstream. Incorrect.Succinic acid to fumaric acid
Succinate dehydrogenase (Complex II) oxidizes succinate + FAD → fumarate + FADH2, embedding FAD in inner mitochondrial membrane for Q-cycle electron transport. Different enzyme. Incorrect.Succinyl CoA to succinic acid
Succinyl CoA synthetase (SUCLG1/SUCLG2) cleaves thioester: Succinyl CoA + GDP + Pi → Succinate + GTP + CoA. Phosphorylated histidine intermediate transfers Pi to GDP. Correct.Succinic acid to α-ketoglutaric acid
Reverses TCA directionality; cycle unidirectional under physiological conditions due to thermodynamics. No mammalian enzyme performs this. Incorrect.Succinyl CoA synthetase TCA cycle reaction represents the sole substrate-level phosphorylation in aerobic respiration, yielding GTP equivalent to ATP without oxidative phosphorylation.
Reaction Mechanism
Mitochondrial α/β heterodimer binds succinyl CoA, displacing CoA via phosphate attack forming succinyl phosphate intermediate. Histidine-246 phosphorylation transfers energy; succinate releases. Phospho-His donates to GDP → GTP. ΔG°’ = -3.4 kJ/mol.
Metabolic Significance
Links TCA anaplerosis (odd-chain fatty acids, propionate, select amino acids) to gluconeogenic entry via oxaloacetate. GTP fuels nucleotide synthesis, protein synthesis (elongation factors). Mutations cause mitochondrial encephalomyopathies (Leigh syndrome).
Cycle Context
Follows α-KG dehydrogenase (NADH producer); precedes succinate dehydrogenase (FADH2, Complex II). Only reversible TCA step under physiological conditions, regulated by [succinyl CoA]/[succinate] ratio, energy charge.
