Inhibition of xanthine oxidase by uric acid and its influence on superoxide radical production.
The inhibition of xanthine oxidase by its reaction product, uric acid, was studied by steady state kinetic analysis. Uric acid behaved as an uncompetitive inhibitor of xanthine oxidase with respect to the reducing substrate, xanthine. Under 50 microM xanthine and 210 microM oxygen, the apparent K(i) for uric acid was 70 microM. Uric acid-mediated xanthine oxidase inhibition also caused an increase in the percentage of univalent reoxidation of the enzyme (superoxide radical production). Steady-state rate equations derived by the King-Altman method support the formation of an abortive-inhibitory enzyme-uric acid complex (dead-end product inhibition). Alternatively, inhibition could also depend on the reversibility of the classical ping-pong mechanism present in xanthine oxidase-catalyzed reactions.
Radi
R
R
Department of Biochemistry, Faculty of Medicine, University of the Republic, Montevideo, Uruguay.
Tan
S
S
Prodanov
E
E
Evans
R A
RA
Parks
D A
DA
D005609:Free Radicals; D007700:Kinetics; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014527:Uric Acid / Q000494:pharmacology*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors*; D014970:Xanthines / Q000494:pharmacology
D005609:Free Radicals; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D014527:Uric Acid; D014969:Xanthine Oxidase; D010100:Oxygen