Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome

Paul A Watkins, Dony Maiguel, Zhenzhen Jia, Jonathan A. Pevsner

Research output: Contribution to journalArticle

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.jlr Knowing the full complement of ACS genes in the human genome will facilitate future studies to characterize their specific biological functions.

Original languageEnglish (US)
Pages (from-to)2736-2750
Number of pages15
JournalJournal of Lipid Research
Volume48
Issue number12
DOIs
StatePublished - Dec 2007

Fingerprint

Coenzyme A Ligases
Human Genome
Genes
Amino Acid Sequence
Amino Acid Motifs
Amino Acids
Proteins
Fatty Acids
Acyl Coenzyme A
COS Cells
Nucleic Acid Databases
Coenzyme A
Chain length
Metabolism
Rodentia
Complementary DNA
Chemical activation
Availability

Keywords

  • Bioinformatics
  • Consensus sequence
  • Conserved motifs
  • Fatty acid activation
  • Fatty acid metabolism
  • Phylogenetic analysis
  • Structure-function

ASJC Scopus subject areas

  • Endocrinology

Cite this

Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. / Watkins, Paul A; Maiguel, Dony; Jia, Zhenzhen; Pevsner, Jonathan A.

In: Journal of Lipid Research, Vol. 48, No. 12, 12.2007, p. 2736-2750.

Research output: Contribution to journalArticle

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