Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism

Aldehydes are highly reactive molecules that are intermediates or products involved in a broad spectrum of physiologic, biologic and pharmacologic pro cesses. Aldehydes are generated from chemically diverse endogenous and exog enous precursors and aldehyde-mediated effects vary from homeostatic and th erapeutic to cytotoxic, and genotoxic. One of the most important pathways f or aldehyde metabolism is their oxidation to carboxylic acids by aldehyde d ehydrogenases (ALDHs). Oxidation of the carbonyl functional group is consid ered a general detoxification process in that polymorphisms of several huma n ALDHs are associated a disease phenotypes or pathophysiologies. However, a number of ALDH-mediated oxidation form products that are known to possess significant biologic, therapeutic and/or toxic activities. These include t he retinoic acid, an important element for vertebrate development, gamma -a minobutyric acid (GABA), an important neurotransmitter, and trichloroacetic acid, a potential toxicant. This review summarizes the ALDHs with an empha sis on catalytic properties and xenobiotic substrates of these enzymes. (C) 2000 Published by Elsevier Science Ireland Ltd.