Kinetic and inhibition studies on reduction of diphenyl sulfoxide by guinea pig liver aldehyde oxidase.
To characterize the properties of diphenyl sulfoxide (DPSO) as a new type of electron acceptor for guinea pig liver aldehyde oxidase (AO), we compared the kinetics of the reductions of DPSO and other classical electron acceptors such as O2 and ferricyanide. The double-reciprocal plot of the 2-hydroxypyrimidine (2-OH PM)-linked DPSO reduction with the highly purified enzyme was biphasic. Similar biphasic plots were obtained with the reductions of other electron acceptors. Only the lower Km value, which was obtained by extrapolation of the plot at lower concentrations of 2-OH PM, was identical with that shown by the freshly prepared crude enzyme. DPSO as well as menadione progressively inhibited the reductions of O2 and ferricyanide with time. Menadione inhibited the DPSO reduction noncompetitively with respect to 2-OH PM and competitively with respect to DPSO, while its mode of inhibition of ferricyanide reduction was uncompetitive for either the electron donor or the acceptor. On the other hand, DPSO showed an uncompetitive and a noncompetitive inhibition of ferricyanide reduction with respect to 2-OH PM and ferricyanide, respectively. These results may indicate that DPSO interacts with the enzyme at the same site as menadione, and thereby when other electron acceptors are present it serves as an actual inhibitor rather than as an electron acceptor for AO.
D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001555:Benzene Derivatives / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008892:Milk / Q000201:enzymology; D010084:Oxidation-Reduction; D014812:Vitamin K / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D001555:Benzene Derivatives; D014812:Vitamin K; C048860:diphenyl sulfoxide; D014969:Xanthine Oxidase; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase