Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1)

Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1), commonly referred to as SCOT, is a vital mitochondrial enzyme that facilitates the utilization of ketone bodies for energy production in extrahepatic tissues (UniProt: P55809). It catalyzes the rate-limiting step of ketolysis by transferring a coenzyme A (CoA) moiety from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA (PubMed: 24561256). This enzyme is highly expressed in the heart, brain, and kidneys, but is notably absent in the liver, preventing the liver from consuming the ketones it synthesizes (StatPearls: Ketogenesis). Mutations in the OXCT1 gene result in SCOT deficiency, a metabolic disorder characterized by recurrent, severe ketoacidosis (NCBI Gene: 5019). Beyond metabolic disorders, OXCT1 is increasingly recognized as a target in oncology, as many cancer types upregulate the enzyme to exploit ketone bodies as a metabolic fuel source under stress (PubMed: 30104618). Although no FDA-approved drugs currently target OXCT1, research into small-molecule inhibitors is ongoing to potentially starve ketone-dependent tumors (PubMed: 28844474).

Other names

3-oxoacid CoA-transferase 1SCOTSuccinyl-CoA:3-oxoacid CoA-transferaseSomatic-type succinyl-CoA:3-oxoacid CoA-transferase

Catalyzes the reversible transfer of the coenzyme A (CoA) moiety from succinyl-CoA to acetoacetate, which is the rate-limiting step in the utilization of ketone bodies (UniProt: P55809).