Acetoacetyl-CoA synthetase (AACS)

Acetoacetyl-CoA synthetase (AACS) is a cytosolic enzyme that catalyzes the ligation of acetoacetate with CoA using ATP, resulting in the production of acetoacetyl-CoA, AMP, and pyrophosphate[2]. It is a key enzyme in the anabolic utilization of ketone bodies, allowing tissues to synthesize cholesterol and fatty acids directly from ketone bodies, bypassing the citrate/ATP citrate lyase pathway. This pathway is particularly important in actively lipogenic tissues such as liver, adipose tissue, mammary gland, skin, intestinal mucosa, adrenals, and brain[2]. AACS is a member of the acyl-CoA synthetase family and is regulated in a tissue-specific manner according to lipid synthesis needs. Its structure and catalytic mechanism involve significant domain motions typical of adenylate-forming enzymes (ANL superfamily). Deficiencies or mutations in related enzymes can cause inherited metabolic disorders, especially those involving ketone body metabolism[3].

Other names

Acetoacetyl-CoA synthetaseAACSACSF1FLJ12389SUR-5Acyl-CoA synthetase family member 1Protein sur-5 homologacetoacetate-CoA ligasehomolog of C. elegans suppressor of ras 5 (sur-5)

Ligase catalysis (conversion of acetoacetate, CoA, and ATP to acetoacetyl-CoA, AMP, and pyrophosphate)