Submitted on August 23, 2007
Accepted on August 30, 2007
Evidence for 26 distinct acyl-CoA synthetase genes in the human genome
Paul A. Watkins, Dony Maiguel, Zhenzhen Jia, and Jonathan Pevsner
Kennedy Krieger Institute, Baltimore, MD 21205
Corresponding Author: watkins{at}kennedykrieger.org
Acyl-CoA synthetases (ACSs) catalyze the fundamental, initial reaction in fatty acid metabolism. “Activation” of fatty acids by thioesterification to coenzyme A allows their participation in both anabolic and catabolic pathways. The availability of the sequenced human genome has facilitated 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 previously demonstrated for twenty proteins, but six remain candidate ACSs. For two candidates, cDNA was cloned, protein expressed in COS-1 cells, and ACS activity 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.
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