The Human Hepatic Cytochromes P450 Involved in Drug Metabolism

Abstract

The cytochromes P450 are a superfamily of hemoproteins that catalyze the metabolism of a large number of xenobiotics and endobiotics. The type and amount (i.e., the animal's phenotype) of the P450s expressed by the animal, primarily in the liver, thus determine the metabolic response of the animal to a chemical challenge. A majority of the characterized P450s involved in hepatic drug metabolism have been identified in experimental animals. However, recently at least 12 human drug-metabolizing P450s have been characterized at the molecular and/or enzyme level. The characterization of these P450s has made it possible to "phenotype" microsomal samples with respect to their relative levels of the various P450s and their metabolic capabilities. The purpose of this review is to compare and contrast the human P450s involved in drug metabolism with their related forms in the rat and other experimental species.

The effect of smoking on postoperative nausea and vomiting

“…A number of environmental chemicals and pollutants, including the polycyclic hydrocarbons present in cigarette smoke, are known to be potent inducers of liver enzymes [14]. These substances are capable of altering the activity of selected human cytochrome P450 isoenzymes, which are responsible for the breakdown and excretion of ingested or inhaled chemicals and toxins [15]. These reactions involve the conversion of metabolites from a hydrophobic form into a more readily excretable hydrophilic form.…”

Modulation of P450-dependent ifosfamide pharmacokinetics: a better understanding of drug activation in vivo

“…Studies with hepatic P450s have shown that P450-catalysed drug metabolism and the regulation of the expression of these xenobiotic-metabolizing enzymes can sometimes be quite different in humans compared with that found in experimental animals (Guengerich, 1989;Wrighton and Stevens, 1992;Nelson et al, 1996). In some cases, different strains within the same species may show differences in the levels of expression of specific P450s (Kraner et al, 1996).…”

Role of the aromatic hydrocarbon receptor in the suppression of cytochrome P-450 2C11 by polycyclic aromatic hydrocarbons

“…At present. the existence of human CYP forms orthologous to constitutive rat CYPs has not been established except in cases such as CYP2E1 and CYP3A subfamiiy forms (Wrighton and Stevens, 1992). Thus extrapolation of regulatory mechanisrns frorn rat to human may not always b8 possible, but in cases where rat and human orthologues clearly exist (GYP1 A1 and CYP2E1 ), mechanisms of CYP regulation appear to be conserved.…”