Primary deuterium isotope effect in the oxidation of an iminium ion by aldehyde oxidase.
Studies of the rates of aldehyde oxidase-mediated oxidation of iminium ion (I) and its specifically labeled counterpart containing deuterium at the methine and methylene carbons of its seven-membered ring (I-d3), are reported. In separate incubations, the isotope effect (kH/kD) on Vmax was 3.3 and that on Km was 1.5. Co-incubation of equimolar amounts of I and I-d3 with aldehyde oxidase resulted in an isotope effect of 2.2 on product ratio. These results support hydrogen transfer from the methine carbon of the seven-membered ring to the molybdenum center of the enzyme as the rate-determining step in the conversion of I to its lactam metabolite (II).
D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000494:pharmacology*; D003903:Deuterium; D007097:Imines / Q000378:metabolism*; D007700:Kinetics; D010084:Oxidation-Reduction
D007097:Imines; D003903:Deuterium; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase