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Acyl-coenzyme A synthetase medium-chain family member 2A (ACSM2A) is a mitochondrial enzyme that catalyzes the activation of medium-chain fatty acids (typically C4–C10) and certain carboxylate-containing xenobiotics by converting them to acyl-CoA thioesters using ATP and CoA as cofactors[4][5][10]. This reaction represents the first, essential step in mitochondrial fatty acid β-oxidation and in the conjugation of xenobiotics for detoxification, such as benzoate and ibuprofen[4][5]. ACSM2A is notably expressed in the kidney, and its activity has been linked to renal metabolic functions and potentially some inherited metabolic diseases[4][5]. It is a member of the adenylate-forming enzyme superfamily, structurally characterized by a specific conformation required for its dual-step catalytic mechanism[1][2].
Drug substrates (e.g. ibuprofen, benzoate) are conjugated via glycine conjugation after initial activation by this enzyme Enzyme catalyzes the formation of acyl-CoA thioesters from medium-chain fatty acids and xenobiotics, enabling their further metabolism or excretion
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