Abstract
Kinetics of the inhibition of two microsomal enzymes of guinea pig liver by SKF 525-A was studied; namely, aryl 4-hydroxylase toward aniline and UDP-glucuronyl transferase toward phenolic glucuronidation of o-aminophenol. In vitro conversion from aniline to p-aminophenol by aryl 4-hydroxylase was noncompetitively inhibited with Ki of 1.7 x 10-4 M, while apparent Km of the reaction was 1.8 x 10-3 M. Excretion of phenol or p-aminophenol in the urine of rats and guinea pigs treated with benzene or aniline, respectively, was markedly decreased by the simultaneous injection of SKF 525-A, indicating the inhibitor was effective in vivo as well as in vitro. Formation of o-aminophenyl glucuronide by UDP-glucuronyl transferase in vitro had apparent Km of 7.1 x 10-5 M, and was inhibited by SKF 525-A also in a noncompetitive manner with Ki of 3.6 x 10-4 M. The in vivo effect of the inhibitor on phenolic glucuronidation was demonstrated with rats and guinea pigs.
ACKNOWLEDGMENTS SKF 525-A was a gift from Smith, Kline and French Laboratories, Philadelphia, Pennsylvania. This work was supported in part by a grant from the Fujiwara Memorial Fund.
- Copyright ©, 1968, by Academic Press Inc.
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