Journal ArticleDOI
The human hepatic cytochromes P450 involved in drug metabolism.
TLDR
The purpose of this review is to compare and contrast the human P 450s involved in drug metabolism with their related forms in the rat and other experimental species with respect to their relative levels of the various P450s and their metabolic capabilities.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.read more
Citations
More filters
Journal ArticleDOI
Lack of electron transfer from cytochrome b5 in stimulation of catalytic activities of cytochrome P450 3A4. Characterization of a reconstituted cytochrome P450 3A4/NADPH-cytochrome P450 reductase system and studies with apo-cytochrome b5.
TL;DR: It is found that apo-b5, devoid of heme, could substitute for b5 in stimulating two prototypic activities, testosterone 6β hydroxylation and nifedipine oxidation, and can facilitate some P450 3A4-catalyzed oxidations by complexing with P4503A4 and enhancing its reduction by NADPH-P450 reductase, without directly transferring electrons to P450.
Journal Article
In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse
TL;DR: Large interspecies differences in the way the selective P450 inhibitors affect the in vitro metabolism of the various substrates in horse, dog, and cat liver microsomes are observed.
Journal ArticleDOI
Cytochrome P450 Isozymes and Antiepileptic Drug Interactions
TL;DR: Recent findings about individual isoforms of the cytochromes P450 involved in the metabolism of phe‐nytoin (PHT) and carbamazepine (CBZ) make prediction of inhibition‐based interactions possible.
Journal ArticleDOI
Diabetes mellitus increases the in vivo activity of cytochrome P450 2E1 in humans.
TL;DR: There was a marked increase in hepatic CYP2E1 activity in obese Type II diabetics as assessed by chlorzoxazone disposition, and increased expression of CYP 2E1 mRNA in peripheral blood mononuclear cells was found in both types of diabetes mellitus.
Journal ArticleDOI
Roles of Cytochromes P450 1A2 and 3A4 in the Oxidation of Estradiol and Estrone in Human Liver Microsomes
TL;DR: Both P450s 1A2 and 3A4 have major roles in oxidations of estradiol and estrone in human liver and that the contents of these two P450 forms in liver microsomes determine which P450 enzymes are most important in hepatic estrogen hydroxylation by individual humans.
References
More filters
Journal ArticleDOI
P450 genes: structure, evolution, and regulation
Journal ArticleDOI
Polymorphic hydroxylation of debrisoquine in man
TL;DR: Family studies supported the view that alicyclic 4-hydroxylation of debrisoquine is controlled by a single autosomal gene and that a defect in this metabolic step is caused by a recessive allele.
Journal ArticleDOI
Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects
TL;DR: The results collectively indicate that P-450 IIE1 is a major catalyst of the oxidation of benzene, styrene, CCl4, CHCl3, CH2Cl2, CH3Cl, 1,2-dichloropropane, ethylene dichloride, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethylcarbamate, and trichloroethylene.
Journal ArticleDOI
Purification and characterization of liver microsomal cytochromes p-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphthoflavone.
TL;DR: The results clearly demonstrate that individual forms of P-450 can be induced by different compounds and that a single compound can lower the level of one form of P -450 while inducing one or more other forms ofP-450.
Related Papers (5)
The Carbon Monoxide-binding Pigment of Liver Microsomes I. EVIDENCE FOR ITS HEMOPROTEIN NATURE
Tsuneo Omura,Ryo Sato +1 more