title: Uncompetitive inhibition of Xenopus laevis aldehyde dehydrogenase 1A1 by divalent cations.
abstract: Aldehyde dehydrogenases (ALDHs) convert aldehydes into their corresponding carboxylic acids. ALDH1A1, also known as ALDH class 1 (ALDH1) or retinaldehyde dehydrogenase (RALDH1), prefers retinal to acetaldehyde as a substrate. To investigate the effects of divalent cations on the dehydrogenase activity of Xenopus laevis ALDH1A1, the formation of acetate and retinoic acid from acetaldehyde and retinal, respectively, was investigated in the presence of Ca2+, Mg2+, Mn2+ or Zn2+. All divalent cations tested inhibited the oxidation of acetaldehyde and retinal by ALDH1A1. When acetaldehyde was used as a substrate, the 50% inhibitory concentrations (IC50) were 10, 24, 35 and 220 microM for Zn2+, Mn2+, Mg2+ and Ca2+, respectively. Kinetic studies of ALDH1A1 dehydrogenase activity in the presence or absence of each cation revealed that the inhibition mode by cations was uncompetitive against acetaldehyde, retinal, and NAD+, and that their inhibitory potencies were greater against acetaldehyde than retinal. It was concluded that the divalent cations inhibited X. laevis ALDH1A1 activity in a substrate-dependent manner by affecting a step of the dehydrogenase reaction that occurred after the formation of the ternary complex of the enzyme, substrate, and coenzyme.
authors.affiliation: Graduate School of Science and Engineering, Shizuoka University, Japan.
authors.forename: Farhana Babli
authors.initials: FB
authors.lastname: Rahman
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamauchi
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D010084:Oxidation-Reduction; D050697:Retinal Dehydrogenase; D012172:Retinaldehyde / Q000378:metabolism; D013379:Substrate Specificity; D014982:Xenopus laevis / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
chemical_list: D002413:Cations, Divalent; D007527:Isoenzymes; D008345:Manganese; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; D050697:Retinal Dehydrogenase; D000079:Acetaldehyde; D008274:Magnesium; D015032:Zinc; D012172:Retinaldehyde; D002118:Calcium