The visible spectrum of a ligand-bound cytochrome P450 is often used to determine the nature of the interaction between the ligand and the P450. One particularly characteristic form of spectra arises from the coordination of nitrogen-containing ligands to the P450 heme iron. These type II ligands tend to be inhibitors because they stabilize the low reduction potential P450 and prevent oxygen bi...

CYP2D6, a xenobiotic metabolizing cytochrome P450 (P450), was found to be present in significant amount on the outer face of cell plasma membrane in addition to the regular microsomal location. Present work demonstrates that this external P450 is catalytically competent and that activity is supported by NADPH-P450 reductase present on the inner face of plasma membrane. Purified plasma membranes...

Drug metabolism in humans is essentially performed by three cytochrome P450 (P450) families (1 to 3), including 23 isoforms. The expression of these P450s is highly variable, and the rate and nature of the metabolites produced depend on the nature and the concentration of individual isoforms. P450 expression pattern is therefore a necessary tool to evaluate the effects of a given drug on P450 e...

(S,S)-3-[3-(Methylsulfonyl)phenyl]-1-propylpiperidine hydrochloride [(-)-OSU6162] is a weak dopamine D2 receptor modulator that possesses potential for the treatment of levodopa (L-DOPA)-induced dyskinesias in patients with Parkinson's disease. In this report, incubations with human liver microsomes revealed that (-)-OSU6162 is selectively metabolized via N-dealkylation to yield N-depropyl (-)-...

A new detection mechanism has been developed for low molecular weight substrate binding to heme proteins based on resonance localized surface plasmon spectroscopy. Cytochrome P450 has strong electronic transitions in the visible wavelength region. Upon binding of a substrate molecule (e.g., camphor), the absorption band of cytochrome P450 shifts to shorter wavelength. The event of camphor bindi...

The effect of changes in the N-terminal membrane-binding domain of cytochrome P450 forms and NADPH-cytochrome P450 reductase types on the cytochrome P450-dependent monooxygenase activities, has been examined. The nifedipine oxidase activity of two human P450 forms (CYP3A4, CYP3A4NF14) which differ only in their primary structure by ten amino acid residues in the N-terminal membrane-binding doma...

The aim of this study was to explore the potential of recombinant cytochrome P450 (P450) enzymes for human metabolic clearance prediction. The relative abundance and relative activity approaches were compared as methods to bridge the gap between catalytic activities in recombinant P450 enzymes and human liver microsomes (HLMs). Relative activity factors were measured by determining the intrinsi...

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its carbonyl-reduction product, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent lung carcinogens in rats and are presumed human lung carcinogens. NNK and NNAL are bioactivated to DNA-binding intermediates via hydroxylation of the carbon atoms adjacent to the nitroso moiety (i.e., alpha-hyd...

Cytochrome P450 monooxygenases (cytochrome P450s), found in virtually all living organisms, play an important role in the metabolism of xenobiotics such as drugs, pesticides, and plant toxins. We have previously evaluated the responses of the oriental migratory locust (Locusta migratoria) to the pyrethroid insecticide deltamethrin and revealed that increased cytochrome P450 enzyme activity was ...

Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse. These chemicals inhibit key drug metabolizing enzymes, such as cytochrome P450 3A4 (CYP3A4).. .. Covera HS, Isoptin SR, Verelan); Warfarin (coumadin); Zolpidem (Ambien): Little or no interaction with grapefruit juice. The aim of this study was to identify the form(s) of cytochrome P450 (CYP) responsibl...