Cytochrome P450 polymorphism--molecular, metabolic and pharmacogenetic aspects. I. Mechanisms of activity of cytochrome P450 monooxygenases.
Cytochrome P450, initially perceived as a type of cell pigment, was soon identified as a hemoprotein with an enzymatic activity characteristic for monooxygenases with an affinity for differentiated endo- or exogenous substrates, including drugs. So far in the human organism 58 CYP isoenzymes belonging to 18 families have been described. Most from the CYP monooxygenases superfamily turned out to be integral elements of hepatocytic reticular monooxygenase complexes which also contain NADPH-dependent cytochrome P450 reductase (CPR). Later investigations indicated the possibility of the participation in electron transport for reticular CYP isoenzymes, alternative NADH-dependent reticular system composed of cytochrome b5 reductase (CBR) and cytochrome b5. The demonstration of the activity of some CYP superfamily isoenzymes not only in hepatocytes but also in many other cells of the human organism, numerous plant and animal tissues and even in cells of fungi, protists and prokaryotes has contributed to the significantly increased understanding of the role of CYP in biological systems. In addition, some CYP isoenzymes were found to be characteristic for the inner mitochondrial membrane monooxygenase complexes which contain NADPH-dependent adrenodoxin reductase (AR) and adrenodoxin (Ad), which is identical with ferredoxin-1 (Fd-1) and hepatoredoxin (Hd).
Pachecka
Jan
J
Department of Biochemistry and Clinical Chemistry, Pharmaceutical Faculty, Medical University of Warsaw, Warsaw, Poland.
Tomaszewski
Piotr
P
Kubiak-Tomaszewska
Grazyna
G
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000201:enzymology; D009249:NADP / Q000378:metabolism; D011110:Polymorphism, Genetic
D007527:Isoenzymes; D009249:NADP; D003577:Cytochrome P-450 Enzyme System