Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial

OXCT1 (succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial), also known as SCOT, is a key mitochondrial enzyme that catalyzes the first rate-limiting step of ketone body catabolism in extrahepatic tissues (UniProt: P55809). It transfers coenzyme A from succinyl-CoA to acetoacetate, producing acetoacetyl-CoA, which is subsequently metabolized to acetyl-CoA for entry into the citric acid cycle. The enzyme functions as a dimer with asymmetric catalytic competence between subunits.

OXCT1 is primarily active in tissues dependent on ketone body oxidation for energy, particularly the brain during fasting or metabolic stress. Genetic deficiency of this enzyme causes succinyl-CoA:3-oxoacid CoA transferase deficiency (SCOTD, MIM 245050), a metabolic disorder characterized by episodic ketoacidosis (UniProt: P55809).

In Alzheimer's Disease, OXCT1 shows ambiguous regulation across subcellular fractions in human post-mortem AD brain compared to age-matched controls (mean log2FC 0.0404), as measured by TMT-labeled proteomics across four subcellular compartments (Chaparral AD proteomics). This minimal average change suggests minimal or differential compartment-specific alterations in ketone metabolism capacity in AD pathology.