Identification of the α-Aminoadipic Semialdehyde Dehydrogenase-Phosphopantetheinyl Transferase Gene, the Human Ortholog of the Yeast LYS5 Gene

摘要: In mammals, L-lysine is first catabolized to alpha-aminoadipate semialdehyde by the bifunctional enzyme synthase (AASS), followed a conversion dehydrogenase. Saccharomyces cerevisiae, which synthesize rather than degrade lysine, latter activity requires two distinct genes. LYS2 encodes reductase activity, while LYS5 phosphopantetheinyl transferase that required activate Lys2p. We have identified full-length human cDNA homologous yeast gene. The contains an open-reading frame of 930 bp predicted encode 309 amino acids, and protein 26% identical 44% similar its counterpart. Northern blot analysis hybridizes single transcript approximately 3 kb in all tissues except testis, where there additional 1.5 kb. Expression highest brain heart skeletal muscle, lesser extent liver. further three genomic BAC clones containing Fluorescence situ hybridization (FISH) using mapped gene chromosome 11q22 alignment sequences allowed partial identification intron-exon boundaries. Finally, one-step recombination S. cerevisiae we generated lys5 knockout strain. Complementation studies demonstrate homolog dehydrogenase activity. hypothesize defects this may result pipecolic acidemia.