title: Characterization of non-enzymatic acylation of amino or thiol groups of bionucleophiles by the acyl-adenylate or acyl-CoA thioester of cholic acid.
abstract: Acyl-adenylates and acyl-CoA thioesters of bile acids (BAs) are highly electrophilic acyl-linked metabolites which can undergo transacylation reactions with amino and thiol groups of nucleophilic groups on acceptor molecules such as amino acids, peptides, and proteins. Here, non-enzymatic acylation at pH 7.4 of glycine, taurine, glutathione (GSH), and N-acetylcysteine (NAC) by cholyl-adenylate (CA-AMP) was compared with that mediated by cholyl-CoA thioester (CA-CoA) using a 1:1 mixture of stable isotopically labeled CA-AMP and unlabeled CA-CoA. The transacylation products of these substrates were analyzed by liquid chromatography/electrospray ionization linear ion-trap mass spectrometry in negative-ion detection mode. CA-AMP was more reactive than CA-CoA with the amino group of glycine or taurine than with the thiol group of GSH or NAC. In contrast, CA-CoA was more reactive than CA-AMP with the thiol group of GSH or NAC and was far less reactive with the amino group of glycine or taurine. These differences in the reactivity of CA-AMP as compared with that of CA-CoA towards amino and thiol groups may be attributed to the electrophilicity of the carbonyl carbon of these acyl-linked cholic acid metabolites and the nucleophilicity of the amino and thiol group in the bionucleophiles that were studied.
authors.affiliation: Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-osaka, 577-8502, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Mitamura
authors.forename: Eriko
authors.initials: E
authors.lastname: Aoyama
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sakai
authors.forename: Takashi
authors.initials: T
authors.lastname: Iida
authors.forename: Alan F
authors.initials: AF
authors.lastname: Hofmann
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000215:Acylation; D000249:Adenosine Monophosphate / Q000737:chemistry*; D019826:Cholic Acid / Q000737:chemistry*; D003065:Coenzyme A / Q000737:chemistry*; D004952:Esters
chemical_list: D004952:Esters; D000249:Adenosine Monophosphate; D019826:Cholic Acid; D003065:Coenzyme A