Succinyl-CoA:3-ketoacid CoA-transferase 1 (SCOT)

Succinyl-CoA:3-ketoacid CoA-transferase 1 (SCOT), encoded by the OXCT1 gene, is a key mitochondrial enzyme essential for the extrahepatic utilization of ketone bodies (UniProt P55809). It catalyzes the rate-limiting step of ketolysis by transferring a coenzyme A (CoA) moiety from succinyl-CoA to acetoacetate, producing acetoacetyl-CoA, which then enters the citric acid cycle for energy production (NCBI Gene 5019). This process is vital for energy homeostasis in tissues with high metabolic demands, such as the brain and heart, especially during fasting or starvation. Genetic mutations leading to a deficiency in SCOT result in a rare metabolic disorder characterized by recurrent episodes of life-threatening ketoacidosis (Fukao et al., 2014). In recent years, SCOT has been identified as a potential therapeutic target in oncology, as certain tumors upregulate this enzyme to exploit ketone bodies as an alternative fuel source to support rapid proliferation (Zhang et al., 2018). While there are currently no FDA-approved drugs targeting SCOT, research into small-molecule inhibitors is ongoing to explore its potential in starving ketolytic cancers, though systemic safety remains a significant concern.

Other names

OXCT13-oxoacid CoA-transferase 1Somatic-type succinyl-CoA:3-oxoacid CoA-transferaseSuccinyl-CoA:3-oxoacid CoA-transferase

Catalyzes the reversible transfer of a coenzyme A (CoA) moiety from succinyl-CoA to acetoacetate, forming acetoacetyl-CoA and succinate, which is the rate-limiting step in ketone body utilization (UniProt P55809).