Oxidative deamination of cyclohexylamine and its homologs by rabbit liver microsomes

Abstract

Cyclohexylamine (CHA) and its homologs, cyclopentylamine (CPA) and cycloheptylamine (CHPA), which formed the type II spectral changes in hepatic microsomes, were deaminated to the corresponding ketones by rabbit liver microsomes in the presence of NADPH and molecular oxygen. The alicyclic ketones were then reduced to the alcohols, of which average percentages in the deaminated products were approximately 75 (CHA), 3 (CPA) and 14 (CHPA). The apparent K m 's for these amines were 5.0 mM (CHA), 4.2 mM (CPA) and 2.1 mM (CHPA), and V max's were 11.0 (CHA), 42.1 (CPA) and 16.4 (CHPA) nmoles/mg protein/30 min. The activity of deamination of these alicyclic primary amines was dependent on both NADPH and oxygen, and inhibited by carbon monoxide, SKF 525A, metyrapone, potassium cyanide and mercuric chloride. These experiments indicate that the deamination of the alicyclic primary amines is catalyzed by a microsomal cytochrome P-450-dependent monooxygenase system in the rabbit liver. Cyclohexanone oxime and other oximes were also identified from the incubation mixtures, and these oximes are suggested as possible intermediates of microsomal deamination of alicyclic primary amines.