Inhibition of p-Aminophenol Metabolism: a Possible Mechanism of Enhancement of Aniline Hydroxylation

The p-hydroxylation of aniline has been traditionally determined by measurement of p-aminophenol (PAP) formation. Comparison of isotopic and colorimetric procedures indicate that the actual amount of aniline metabolized exceeds the amoung of PAP recovered. Data suggest that enhancement of p-hydroxylation of aniline by acetone, malaoxon and paraoxon may result from inhibition of further metabolism of PAP by the microsomal cytochrome b5-dependent desaturase system, involvement of the desaturase system is supported by observations that: (a) metabolism of PAP was reduced by starvation and stimulated when starvation was followed by feeding a high carbohydrate diet; (b) enrichment of hepatic microsomes with detergent purified cytochrome b5 decreased the amount of aniline apparently metabolized, as measured by the amount of PAP recovered, and (c) a high correlation occurred between effects of acetone, malaoxon and paraoxon on reoxidation of cytochrome b5 and capacity of these three compounds to enhance aniline metabolism.