Cytochrome P450 activity

Ekins S, De Groot MJ, Jones JP. Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome P450 active sites. Drug Metab Dispos 2001 29 936-44. 

Organic peroxides such as cumene hydroperoxide and t-butyl hydroperoxide have extensively been used as experimental agents. They provoke lipid peroxidation in hepatocytes, probably by the generation of alkoxyl and peroxyl radical intermediates after reaction with cytochrome P450. Other cytotoxic mechanisms are probably involved including protein thiol and non-protein thiol oxidation and deranged calcium homeostasis (Jewell et al., 1986). In fact, the addition of cumene hydroperoxide to isolated bUe duct cells, devoid of cytochrome P450 activity, still results in cell death but lipid peroxidation is not detectable (Parola et al., 1990). 

Owing to the fact that ethyl ethers are especially effective substrates for CYP1A1 [184], the probe possesses an ethyl group on the phenolic oxygen of the trimethyl lock. In vitro, fluorescence was manifested by CYP1A1 isozyme with Kcat/KM 8.8 x 103 M-1s 1 and KM 0.09 pM. In cellulo, the probe revealed the induction of cytochrome P450 activity by the carcinogen 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD), and its repression by the chemoprotectant resveratrol. 

Yatzeck MM, Lavis LD, Chao T-Y et al (2008) A highly sensitive fluorogenic probe for cytochrome P450 activity in live cells. Bioorg Med Chem Lett 18 5864—5866... 

L The answer is d. (Hardman, p 906.) Cimetidine slows the metabolism of Ca channel blockers, which are substrates for hepatic mixed-function oxidases. Inhibition of cytochrome P450 activity is peculiar to cimetidine and is not a mechanism of action of other histamine 2 (Hz) blockers. 

Janz, D.M., T.L. Metcalfe, C.D. Metcalfe, and G.D. Haffner. 1992. Relative concentrations of cytochrome P450-active organochlorine compounds in liver and muscle of rainbow trout from Lake Ontario. Jour. Great Lakes Res. 18 759-765. 

Zhu, B., et al., "Assessment of Cytochrome P450 Activity by a Five-Drug Cocktail Approach," Clin. Pharmacol. Ther., 70, 455-461 (2001). 

CYP2E1. Chronic exposure of rats to ethanol leads to enhanced cytochrome P450 activity. After discovery of the phenomenon, the enhanced activity was soon characterized... 

Walsky, R.L. and Obach, R.S. (2004) Validated assays for human cytochrome P450 activities. Drug Metabolism and Disposition, 32 (6), 647—660. 

Korzekwa, K.R., Krishnamachary, N., Shou, M., Ogai, A., Parise, R.A., Rettie, A.E., Gonzalez, F.J. and Tracy, T.S. (1998) Evaluation of atypical cytochrome P450 kinetics with two-substrate models evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry, 37 (12), 4137-4147. 

Steckelbroeck S, Heidrich DD, Stoffel-Wagner B, Hans VH, Schramm J, et al. 1999. Characterization of aromatase cytochrome P450 activity in the human temporal lobe. J Clin Endocrinol Metab 84 2795-2801. 

Gartner, C. A. (2003) Photoaffinity ligands in the study of cytochrome p450 active site structure. Curr. Med. Chem. 10, 671-689. 

Shou, M., Grogan, J., Mancewicz, J. A., et al. (1994) Activation of CYP3A4 Evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 33, 6450-6455. 

Cytochromes P450 activity Reduced Increased Slightly increased... 

A. Diazepam is metabolized in the liver by CYP3A4 and CYP2C19 efavirenz inhibits both of these isozymes and is likely to increase plasma levels of diazepam. Diazepam is almost completely converted to inactive metabolites therefore, renal elimination is not much of a concern. Lamivudine may produce fatigue as a side effect but does not potentiate the depressant activity of diazepam. Zidovudine does not induce cytochrome P450 activity, and diazepam does not have to be converted to an active form for sedative activity. 

The antimutagenic effect of EOs of Helichrysum italicum, Ledum groenlandi-cum and Ravensara aromatica could be explained by the interaction of their constituents with cytochrome P450 activation involving in the detoxification system [367]. 

Formaldehyde generated from nitromethane was found only in trace amounts after incubation with microsomes from from Fischer 344 rat liver, but none was found after incubation with rat nasal microsomes (Dahl Hadley, 1983). Nitromethane inhibited rabbit liver cytochrome P450 activity, apparently competing for the same ferrohaemo-chrome-binding sites as carbon monoxide (Wade et al, 1977). 

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