THE INHIBITION OF THE URIDINE DIPHOSPHATE-TRANSGLUCURONYLASE ACTIVITY OF MOUSE-LIVER HOMOGENATES BY THIOL REAGENTS

Abstract

A study of the catalysis of the formation of the glucuronides of o-aminophenol and p-nitrophenol by the uridine diphosphate transglucuronylase of homogenates of female mouse liver has been made, with reference to the effect of reagents reacting with thiol groups. The synthesis of both glucuronides was completely inhibited by organic mercurials and N-ethylmaleimide. The inhibition was only partial with arsenite and the arsenoxides, iodo-acetamide and o-iodosobenzoate. The o-aminophenol system was much more sensitive than that for p-nitrophenol to all the thiol reagents, except N-ethylmaleimide, which was equally active in both systems. At very low concentrations of the organic mercurials, the o-amino-phenol system was activated. With o-aminophenyl glucuronide formation, complete protection was given by glutathione and cysteine against the organic mercurials, N-ethylmaleimide and iodoacetamide, and partial protection against the arsenicals. Reversal was complete against the mercurials, and very limited against the arsenicals and iodoacetamide. The effects of N-ethylmaleimide and o-iodosobenzoate were irreversible. Results with p-nitrophenol were very similar. Uridine diphosphate transglucuronylase was partially protected against p-chloromercuribenzoate and lewisite oxide by uridine diphosphate glucuronate, but not by o-aminophenol. Glutathione did not prevent the decline in the rate of conjugation of o-aminophenol when homogenates were aged by incubation at 30[degree]. Cysteine was unable to prevent or reverse inactivation by ultrasonic radiation.