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succinyl CoA synthetase

BiochemistryCitric acid cycleSubstrate-level phosphorylation

Summary

Succinyl CoA synthetase is the citric acid cycle enzyme that converts succinyl CoA to succinate and uses the released thioester energy to make GTP (or ATP, depending on the isoform) from GDP (or ADP) and Pi. It is the cycle's substrate-level phosphorylation step, not oxidative phosphorylation.

Detail

Meaning: Succinyl CoA synthetase catalyzes step 5 of the citric acid cycle. Cleaving the high-energy thioester bond of succinyl CoA releases enough energy to attach inorganic phosphate to GDP, making GTP. This is substrate-level phosphorylation: phosphate is added using energy from a substrate, with no electron transport chain or proton gradient involved. Textbooks usually show GTP. Some tissues have an isoform that makes ATP from ADP. Nucleoside diphosphate kinase can interconvert the two (GTP + ADP ⇌ GDP + ATP).

Equation: succinyl CoA + Pi + GDP → succinate + CoA + GTP. Pi is inorganic phosphate, GDP and GTP are guanosine di- and triphosphate, and CoA is coenzyme A. Amounts are in mol.

On the MCAT: Expect questions that ask which cycle step directly yields a nucleoside triphosphate, or that ask for the total per glucose (two turns give two GTP or ATP). The enzyme sits after α-ketoglutarate dehydrogenase, which makes succinyl CoA, and before succinate dehydrogenase, which uses FAD. If a passage inhibits or removes the enzyme, predict that succinyl CoA builds up and downstream intermediates (succinate, fumarate, malate) fall.

Common confusion: Students call this oxidative phosphorylation, or think the cycle makes most of its ATP here. It makes only one GTP or ATP per turn, directly, and most ATP comes later from NADH and FADH₂ through the electron transport chain. The name "synthetase" reflects the reverse reaction, which builds succinyl CoA using NTP energy. In the cycle the reaction runs forward and makes the NTP.

Sources

  • Lehninger Principles of Biochemistry
  • Biochemistry (Berg, Tymoczko, Stryer)
  • Biochemistry (Voet and Voet)

Written for the MCAT and checked before it was published. For study reference only. Spotted an error? Let us know.