ACAT1 and metabolic disease: Mitochondrial acetyl-CoA acetyltransferase (ACAT1), the first purified thiolase located in the mitochondrial matrix,24,25 functions in both synthetic and degradative pathways to catalyze the Claisen condensation of two molecules of acetyl-CoA into acetoacetyl-CoA or the reverse reaction of acetoacetyl-CoA into two molecules of acetyl-CoA, thus participating in isoleucine degradation, ketogenesis, ketolysis, and fatty acid oxidation.26,27 Therefore, ACAT1 deficiency often leads to an autosomal recessive inherited metabolic disorder.