Which enzyme catalyzes the substrate-level phosphorylation to form GTP (or ATP) in the Krebs cycle?

• A. Succinyl-CoA synthetase
• B. Isocitrate dehydrogenase
• C. Malate dehydrogenase
• D. α-Ketoglutarate dehydrogenase

Answer: (A)

The main idea is that the Krebs cycle includes a step where a high-energy phosphate is transferred directly to a nucleotide, producing GTP (or ATP) without using the electron transport chain. This substrate-level phosphorylation happens when succinyl-CoA is converted to succinate. The enzyme doing this is succinyl-CoA synthetase (also called succinyl-CoA thiokinase). It captures the energy from the thioester bond of succinyl-CoA and transfers a phosphate to GDP to form GTP (or to ADP to form ATP, depending on the tissue).

The other enzymes listed drive oxidative steps that generate NADH (and release CO2) rather than forming a nucleotide phosphate: isocitrate dehydrogenase, malate dehydrogenase, and α-ketoglutarate dehydrogenase all contribute electrons to carriers but do not perform substrate-level phosphorylation. In some tissues, the GTP produced can be readily converted to ATP as needed, via a phosphotransferase pathway, but the direct phosphorylation step itself is specific to succinyl-CoA synthetase.