Factors affecting the relative importance of amine oxidases and monooxygenases in the in vivo metabolism of xenobiotic amines in humans.
The monooxygenases and the amine oxidases (AOs) are the major enzyme systems involved in vivo in the oxidative metabolism of xenobiotic amines in humans. With the exception of the inhibition of the metabolism of tyramine ingested by subjects taking inhibitors of MAO-A or of both MAO-A and -B, which has been extensively investigated, the involvement of the monoamine oxidases in xenobiotic amine metabolism (drugs in particular) has been largely neglected. Furthermore, with the exception of amlodipine, there have been essentially no studies on the metabolism of drug amines by amine oxidases such as SSAOs and PAOs in humans. In contrast, monooxygenases (CYP isoenzymes, and to a lesser extent, FMOs) have been extensively investigated in terms of their involvement in xenobiotic metabolism. It is possible that the contribution of AOs to the overall metabolism of xenobiotic amines in humans has been underestimated, or erroneously estimated, as most investigations of drug metabolism have been performed using in vitro test systems optimized for CYP activity, such as liver microsomes, and most investigations of drug metabolism in vivo in humans have identified only the final, stable metabolites.
Strolin Benedetti
M
M
UCB Pharma, Non Clinical Development, Nanterre, France. margherita.strolin@ucb-group.com
Tipton
K F
KF
Whomsley
R
R
Baltes
E
E
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic / Q000502:physiology*; D008862:Microsomes, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism
D000588:Amines; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D001189:Aryl Hydrocarbon Hydroxylases; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase