Substrate specificities and functions of the P450 cytochromes.
Currently, the major recognized biochemical functions of members of the large superfamily of P450 hemoproteins (referred to commonly as the cytochromes P450) include catalyses of the monooxygenations of a wide variety of endogenous and exogenous lipophilic chemicals. Substrates that have attracted the greatest attention thus far are steroids, fatty acids, eicosanoids, retinoids, other endogenous lipids, therapeutic agents, pesticides/herbicides, chemical carcinogens, industrial chemicals and other environmental contaminants and toxic xenobiotic organics of low molecular weight. Commonly, monooxygenation of such substrates results in the generation of metabolites capable of producing biological effects that are profoundly different (qualitatively as well as quantitatively) from those elicitable by the parent chemical per se. P45OXIX-dependent conversion of testosterone to estradiol-17 beta provides a dramatic example. Thus, these hemoproteins serve as extremely important but, as yet, largely unpredictable regulators of the biological effects producible by endobiotics as well as by xenobiotics. Current focus is on the identification and acquisition of sequence information on hereto unidentified and/or uncharacterized P450 isoforms and ascertainment of the specific functions of specific, individual isoforms. The regulation of quantities and activities of such isoforms in specific species/tissues, understandably, is also of great current interest. This interest has been further intensified by recent results indicating that substrate specificity associated with one P450 may not be the same as the corresponding isoform derived from a different animal species. Recent technological advances promise to greatly hasten the acquisition of knowledge concerning the functions of these important hemoproteins.
Juchau
M R
MR
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D013379:Substrate Specificity
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System