Some aspects of the role of cytochrome P‐450 isozymes in the n‐oxidative transformation of secondary and tertiary amine compounds

Publisher Website
Google Scholar
Abstract
Indirect evidence of the participation of cytochrome P‐450 (P‐450) in the microsomal N‐oxygenation of secondary and tertiary nitrogen functions is presented by studies employing diagnostic modifiers of the hemoprotein system as well as antibodies directed toward the diverse P‐450 isoforms and NADPH‐cytochrome P‐450 reductase. Experiments with recombinant hemoproteins or P‐450 isozymes directly purified from the tissues of various animal species support the results obtained by the inhibitor assays. Although the intermediacy of aminium radicals is thought to be restrictive to P‐450‐catalyzed N‐oxygenation of secondary and tertiary amine groups bearing accessible hydrogens on the α‐carbon, numerous exceptions to this rule are documented. It is proposed that aminium radicals partition between oxygen rebound and α‐hydrogen abstraction to yield a finite level of N‐oxygenated product in all P‐450‐mediated amine oxidations, the partition ratio depending on the amine structure and particular P‐450 isozyme operative. In some instances, N‐oxygenation appears to proceed by peroxidatic mechanisms. The relative contribution of P‐450 to the N‐oxygenation of secondary and tertiary amines in crude preparations or live animals, where competition with the flavin‐containing monooxygenase (FMO) occurs, seems to be a function of the relative amounts and catalytic capacities of the two enzyme systems. Both parameters are species and tissue dependent. Accordingly, the extent to which P‐450 contributes to total N‐oxidative turnover of the amine substrates varies from minor to major. © 1996 John Wiley & Sons, Inc.

This publication has 59 references indexed in Scilit: