Aminoadipate-semialdehyde dehydrogenase (AASDH)

Aminoadipate-semialdehyde dehydrogenase (AASDH) is a human enzyme encoded by the AASDH gene, also known as acyl-CoA synthetase family member 4 (ACSF4), and is found in various tissues, with high expression in the liver[3][7]. This enzyme is part of the non-ribosomal peptide synthetase family and contains an AMP-binding (adenylation) domain, a phosphopantetheine-binding domain, and a pyrroloquinoline quinone (PQQ) binding domain[3][4][7]. Functionally, it is involved in lysine catabolism, specifically catalyzing a key step in the conversion of L-2-aminoadipate 6-semialdehyde to L-2-aminoadipate, using NAD+ or NADP+ as a cofactor, and is part of both lysine biosynthesis and degradation pathways[5][1]. Additionally, it has been demonstrated to bind beta-alanine in an ATP-dependent manner, forming a thioester intermediate, suggesting a role in beta-alanine activation and possibly rare post-translational or post-transcriptional modifications[2][4][6]. Clinically, mutations in the AASDH gene are associated with hyperlysinemia, an inherited metabolic disorder characterized by increased lysine levels, which can be asymptomatic or present with a spectrum of symptoms. The enzyme does not appear to be a current therapeutic target and no drugs are known to interact specifically with AASDH[1][7][4].

Other names

Beta-alanine-activating enzymeACSF4U26HSPC318NRPS998LYS2NRPS1098Acyl-CoA synthetase family member 4Protein NRPS998acyl-CoA synthetase family member 4non-ribosomal peptide synthetase 1098non-ribosomal peptide synthetase 9982-aminoadipic 6-semialdehyde dehydrogenasealpha-aminoadipate semialdehyde synthaselysine-ketoglutarate reductase/saccharopine dehydrogenasesaccharopine dehydrogenase (NAD(+), L-glutamate-forming)saccharopine dehydrogenase (NADP(+), L-lysine-forming)LKR/SDHLKRSDHLORSDH