title: Monovalent cation effects on the activity of the xenobiotic/medium-chain fatty acid:CoA ligases are substrate specific.
abstract: The effect of monovalent cation on the activity of the XL-I and XL-III forms of xenobiotic/medium-chain fatty acid:CoA ligase (XM-ligase) was investigated using a variety of different carboxylic acid substrates. With benzoate or p-hydroxybenzoate as substrate, the XL-I ligase was essentially inactive in the absence of monovalent cation. However, with phenylacetic acid and medium-chain fatty acids as substrate, the enzyme retained 3 to 10% activity upon removal of monovalent cation. Further, while Na+ was ineffective with benzoate and p-hydroxybenzoate as substrates, it was effective with other substrates, although still less effective than K+. For XL-III, activity toward benzoate, hydroxybenzoate, and salicylate was insignificant in the absence of monovalent cation, but this rate was 10% of the K(+)-supported rate for hexanoate and 20% for decanoate. Also, with decanoate as substrate, XL-III was activated more by Na+ than by K+. Thus, the nature of the dependence on monovalent cation for activity is substrate-selective. Kinetic analysis of the effect of K+ on the activity of XL-I and XL-III revealed that activation by K+ was not the result of alteration of the affinity of the enzymes for either ATP or the carboxylic acid. For both forms of XM-ligase, K+ was found to enhance the affinity of the enzyme for CoA, regardless of the substrate, although the extent of the enhancement was substrate-specific. In almost all cases there was further activation, even at saturating concentrations of CoA, which indicates an additional effect of monovalent cation on the catalytic rate constant for the reaction. The exception was activation of XL-III activity toward decanoate, which was solely the result of enhanced binding affinity for CoA.
authors.affiliation: Department of Veterans' Affairs Medical Center, San Francisco, CA 94121, USA. vessey.donald a@sanfrancisco.va.gov
authors.forename: D A
authors.initials: DA
authors.lastname: Vessey
authors.forename: M
authors.initials: M
authors.lastname: Kelley
authors.forename: E
authors.initials: E
authors.lastname: Lau
authors.forename: S Z
authors.initials: SZ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002414:Cations, Monovalent; D002417:Cattle; D003066:Coenzyme A Ligases / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D002414:Cations, Monovalent; D015262:Xenobiotics; D003066:Coenzyme A Ligases; C107128:xenobiotic medium chain fatty acid - coenzyme A ligase