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

Ketone body utilization, or ketolysis, is the critical metabolic process by which extrahepatic tissues convert circulating ketone bodies into energy. The primary target molecule within this pathway is Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1), the rate-limiting enzyme that catalyzes the transfer of coenzyme A from succinyl-CoA to acetoacetate (NCBI Gene, 2023). While the liver produces ketones (ketogenesis), it lacks OXCT1, ensuring that ketones are exported to vital organs like the brain, heart, and skeletal muscle where they enter the TCA cycle as acetyl-CoA (StatPearls, 2023). In oncology, OXCT1 is often upregulated by certain tumors (e.g., glioblastoma, breast cancer) to provide a survival advantage in nutrient-deprived environments, making it an emerging target for metabolic inhibition (PubMed, 2020). Conversely, in cardiovascular research, enhancing this pathway is explored as a means to improve myocardial efficiency in the failing heart, which may shift its fuel preference toward ketones (Nature Metabolism, 2021). Although specific small-molecule inhibitors of OXCT1 are largely in the experimental phase, the pathway is frequently modulated through ketogenic diets and SGLT2 inhibitors in clinical settings.

Other names

SCOTSuccinyl-CoA:3-oxoacid CoA transferase3-oxoacid CoA-transferase 1Ketone body utilization pathwayKetolysis pathway

Drugs targeting this pathway typically aim to inhibit or enhance the enzymatic conversion of acetoacetate to acetoacetyl-CoA, the rate-limiting step in ketolysis catalyzed by OXCT1.