Differential properties of the microsomal deamination and hydroxylation reactions

Abstract

The addition of 1 mM of the metal complexing reagents such as EDTA, alpha, alpha'-dipyridyl, 1,10-phenanthroline and Tiron to the incubation of benzylamine, aminopyrine, p-nitroanisole and aniline, respectively, inhibited selectively the microsomal deamination of benzylamine, whereas the addition of the monoamine oxidase inhibitors tranylcypromine, nialamide and iproniazid specifically decreased the metabolism of aminopyrine, p-nitroanisole and aniline. Pretreatment of rats with 3,4-benzpyrene or phenobarbital increased the liver microsomal concentration of cytochrome P-450 (448) and the rate of aminopyrine and p-nitroanisole demethylation and of aniline hydroxylation whereas pretreatment cytochrome P-450 depressor agents such as cadmium or cobalt lowered the concentration of the hemoprotein and decreased the rate of the demethylation reactions. Phenobarbital and 3,4-benzpyrene pretreatment had either no effect or decreased significantly the rate of the microsomal deamination reaction respectively. The administration of cadmium slightly decreased the rate of benzylamine deamination whilst cobalt produced no significant effect. These results indicate that the microsomal oxidative deamination reaction has different properties than the dealkylation and aromatic hydroxylation reactions, thus suggesting a different enzyme system.