title: Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome.
abstract: Acyl-coenzyme A synthetases (ACSs) catalyze the fundamental, initial reaction in fatty acid metabolism. "Activation" of fatty acids by thioesterification to CoA allows their participation in both anabolic and catabolic pathways. The availability of the sequenced human genome has facilitated the investigation of the number of ACS genes present. Using two conserved amino acid sequence motifs to probe human DNA databases, 26 ACS family genes/proteins were identified. ACS activity in either humans or rodents was demonstrated previously for 20 proteins, but 6 remain candidate ACSs. For two candidates, cDNA was cloned, protein was expressed in COS-1 cells, and ACS activity was detected. Amino acid sequence similarities were used to assign enzymes into subfamilies, and subfamily assignments were consistent with acyl chain length preference. Four of the 26 proteins did not fit into a subfamily, and bootstrap analysis of phylograms was consistent with evolutionary divergence. Three additional conserved amino acid sequence motifs were identified that likely have functional or structural roles. The existence of many ACSs suggests that each plays a unique role, directing the acyl-CoA product to a specific metabolic fate. Knowing the full complement of ACS genes in the human genome will facilitate future studies to characterize their specific biological functions.
authors.affiliation: Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. watkins@kennedykrieger.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Watkins
authors.forename: Dony
authors.initials: D
authors.lastname: Maiguel
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Jia
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pevsner
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D003066:Coenzyme A Ligases / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment
chemical_list: D003066:Coenzyme A Ligases