title: Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.
abstract: BACKGROUND
  Activation of fatty acids by the acyl-CoA synthetases (ACSs) is the vital first step in fatty acid metabolism. The enzymatic and physiological characterization of the human xenobiotic/medium chain fatty acid: CoA ligases (ACSMs) has been severely neglected even though xenobiotics, such as benzoate and salicylate, are detoxified through this pathway.
  
  
  METHODS
  This review will focus on the nomenclature and substrate specificity of the human ACSM ligases; the biochemical and enzymatic characterization of ACSM1 and ACSM2B; the high sequence homology of the ACSM2 genes (ACSM2A and ACSM2B) as well as what is currently known regarding disease association studies.
  
  
  CONCLUSIONS
  Several discrepancies exist in the current literature that should be taken note of. For example, the single nucleotide polymorphisms (SNPs) reported to be associated with aspirin metabolism and multiple risk factors of metabolic syndrome are incorrect. Kinetic data on the substrate specificity of the human ACSM ligases are non-existent and currently no data exist on the influence of SNPs on the enzyme activity of these ligases. One of the biggest obstacles currently in the field is that glycine conjugation is continuously studied as a one-step process, which means that key regulatory factors of the two individual steps remain unknown.
authors.affiliation: a Centre for Human Metabolomics, Biochemistry Division , North-West University , Potchefstroom , South Africa.
authors.forename: Rencia
authors.initials: R
authors.lastname: van der Sluis
authors.affiliation: a Centre for Human Metabolomics, Biochemistry Division , North-West University , Potchefstroom , South Africa.
authors.forename: Elardus
authors.initials: E
authors.lastname: Erasmus
mesh_terms: D000818:Animals; D001241:Aspirin / Q000009:adverse effects / Q000378:metabolism*; D019817:Benzoic Acid / Q000009:adverse effects / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D013379:Substrate Specificity; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D015262:Xenobiotics; D019817:Benzoic Acid; D003066:Coenzyme A Ligases; D001241:Aspirin
keywords: ACSM; CoA ligase; acyl-coenzyme A; aspirin; benzoate; glycine conjugation; medium chain fatty acid; salicylate