succinylCoAsyntetas

Succinyl-CoA synthetase, also known as succinyl-CoA thiokinase, is a mitochondrial matrix enzyme of the citric acid cycle that catalyzes the conversion of succinyl-CoA to succinate while generating a nucleotide triphosphate. This reaction provides substrate-level phosphorylation within the cycle and helps link fatty acid and carbohydrate metabolism to energy currency.

The core reaction can proceed in two ways depending on the isoform: succinyl-CoA + GDP + Pi ⇌ succinate + CoA-SH + GTP, or succinyl-CoA + ADP + Pi ⇌ succinate + CoA-SH + ATP. In both cases, a high-energy phosphoryl group is transferred to a nucleotide. The enzyme operates via a phosphohistidine intermediate during the transfer of the phosphate to the nucleotide.

In humans, the enzyme is a heteromeric complex formed by a beta-subunit (encoded by SUCLG1) and an alpha-subunit encoded by either SUCLA1 or SUCLA2. The SUCLA1-containing form is the ATP-forming variant, while the SUCLA2-containing form is the GTP-forming variant. This dual isoform arrangement allows tissue-specific generation of ATP or GTP as needed. In bacteria, a related succinyl-CoA synthetase comprises SucC and SucD subunits and performs a similar substrate-level phosphorylation step in the TCA cycle.

Location and context: within the mitochondrial matrix, often associated with the inner mitochondrial membrane, and, in prokaryotes, in the cytosol as part of the TCA cycle. Its activity is essential for efficient energy metabolism and for supplying nucleotide triphosphates during respiration.