Characterization of the human gene encoding α-aminoadipate aminotransferase (AADAT)

Abstract In mammals, the conversion of α-aminoadipate to α-ketoadipate by α-aminoadipate aminotransferase (AADAT) is an intermediate step in lysine degradation. A gene encoding for α-aminoadipate aminotransferase and kynurenine aminotransferase activites had been previously identified in the rat ( KAT/AadAT ). We identified the human gene ( AADAT ) encoding for AADAT. It has a 2329 bp cDNA, a 1278 bp open-reading frame, and is predicted to encode 425 amino acids with a mitochondrial cleavage signal and a pyridoxal-phosphate binding site. AADAT is 73% and 72% identical to the mouse and rat orthologs, respectively. The genomic structure spans 30 kb and consists of 13 exons. FISH studies localized the gene to 4q32.2. Two transcripts (∼2.9 and ∼4.7 kb ) were identified, with expression highest in liver. Bacterial expression studies confirm that the gene encodes for AADAT activity. The availability of the DNA sequence and enzyme assay will allow further evaluation of individuals suspected to have defects in this enzyme.