Human cytochromes P-450.
Studies in vivo have provided evidence for a multiplicity of cytochromes P-450 in man, some of which are under independent monogenic control. Although the activity of cytochromes P-450 in man are generally lower than those of rat, this is by no means always the case. There are several important exceptions including the N-hydroxylation of 2-acetamidofluorene. Studies in vitro by a number of different techniques have confirmed the evidence from studies in vivo that there are multiple forms of human cytochrome P-450. In addition to differences in Vmax, the different forms of cytochrome P-450 may also exhibit marked differences in their apparent Km values. The implications that this may have for pharmacokinetics and toxicology are discussed. The polymorphism in the 4-hydroxylation of debrisoquine observed in vivo has been shown to be due to a defect in a specific form of cytochrome P-450 which appears to be under monogenic regulation. Cross-inhibition studies have enabled the specificity of this isozyme to be characterized. Such studies have also enabled the contribution of this isozyme of cytochrome P-450 to the oxidation of other substrates to be determined. Compounds investigated include bufuralol and phenytoin. Evidence from studies both in vivo and in vitro suggest that selective induction of different forms of cytochrome P-450 can occur in man. However, the number of different classes of inducer in man is not yet known. Human cytochromes P-450 have been purified to near homogeneity in several laboratories. Different forms of cytochrome P-450 purified from the same liver sample vary in molecular weight, chromatographic characteristics and substrate specificities.
D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D004790:Enzyme Induction; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008967:Molecular Biology; D004364:Pharmaceutical Preparations / Q000378:metabolism; D012907:Smoking; D013045:Species Specificity
D007527:Isoenzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases