Cytochrome P450 polymorphism--molecular, metabolic, and pharmacogenetic aspects. II. Participation of CYP isoenzymes in the metabolism of endogenous substances and drugs.
In the human organism 58 cytochrome P450 (CYP) isoenzymes belonging to 18 families have been described. These hemoproteins, with enzymatic activity characteristic for monooxygenases, show a broad affinity for chemically differentiated endo- or exogenous compounds, including drugs. CYP isoenzymes participate in metabolic pathways important for proper physiological functioning of the human organism, i.e.: cholesterol, bile acid and oxysterol biosynthesis; metabolism of fatty acids, prostaglandins, prostacyclins, leukotrienes, steroid hormones, ketone bodies, vitamines A and D. CYP isoenzymes participate in the metabolism of over 80% of drugs and other xenobiotic substances which can be present in the human organism. Differences in molecular structure and kinetics of conformational changes of particular isoenzymes of CYP superfamily monooxygenases on the one hand determine their affinity direction for chemically differentiated groups of compounds susceptible to oxidation, on the other hand determine the mechanism and position of the oxidative change of their molecules. Drugs and their metabolites and other endogenous and xenobiotic compounds may be acting not only as substrates, but also as competitive and non- competitive inhibitors, suicide inhibitors and inducers of CYP isoenzymes as well as repressors of CYP genes. These relationships are the metabolic basis of numerous multidirectional interactions between drugs, drug metabolites, food components, stimulants, environmental toxins and metabolites of these xenobiotics.
Tomaszewski
Piotr
P
Department of Biochemistry and Clinical Chemistry, Pharmaceutical Faculty, Medical University of Warsaw, Warsaw, Poland. piotrtomaszewski@poczta.onet.pl
Kubiak-Tomaszewska
Grazyna
G
Pachecka
Jan
J
D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004347:Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic; D015262:Xenobiotics / Q000378:metabolism*
D007527:Isoenzymes; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System