From the Research
The GTP production in the TCA cycle occurs during the succinyl-CoA to succinate conversion, catalyzed by the enzyme succinyl-CoA synthetase (also called succinate thiokinase), as supported by the most recent study 1. This step is crucial as it captures the energy released from breaking the high-energy thioester bond in succinyl-CoA to generate GTP from GDP and inorganic phosphate. The importance of this reaction lies in its role as the only step in the TCA cycle that directly produces a high-energy phosphate compound through substrate-level phosphorylation, as noted in 2. Key aspects of this process include:
- The energy from the thioester bond is used to generate GTP, which is energetically equivalent to ATP and can be readily converted to ATP by the enzyme nucleoside diphosphate kinase, as discussed in 3.
- The succinyl-CoA to succinate conversion is the fifth step in the TCA cycle, occurring after the decarboxylation of α-ketoglutarate and before the oxidation of succinate to fumarate.
- The GTP produced plays a significant role in mitochondrial metabolism and can serve as an important molecular signal of TCA-cycle activity, as suggested by 4. Overall, the production of GTP during the succinyl-CoA to succinate conversion is a vital component of the TCA cycle, contributing to energy production and mitochondrial function, as highlighted by the structural basis of succinyl-CoA synthetase 1.