Urease Catalysis. Ii. Inhibition of the Enzyme by Hydroxyurea, Hydroxylamine, and Acetohydroxamic Acid.

In the preceding paper (l), hydroxyurea was shown to be a substrate for urease and to be associated with the development of a marked inhibition of the enzyme during t,he course of the reaction. The lack of significant inhibition during the hydrolysis of urea at equal concentrations suggested that the hydroxylamine formed during hydroxyurea hydrolysis was the responsible agent. The inhibitory effects of both compounds are here extended to urea hydrolysis and found to differ significantly. Hydroxylamine has previously been shown to inhibit some but not all sulfhydryl-dependent enzymes, and it had been presumed that this effect resulted from nonspecific oxidation of -SH groups to the disulfide form (2). The studies reported below indicate, however, that this is not the mechanism by which hydroxylamine inhibits urease. The inhibit.ory effects of hydroxyurea also led to the exploration of inhibition by acetohydroxamic acid, which is not hydrolyzed by urease (1). This compound was found to be a potent and irreversible inhibitor of the enzyme.