Xenobiotic metabolism cytochromes

Xenobiotics metabolism, 1, 223-225 monooxygenation cytochrome P450 in, 1, 259-260 Xenon... 

Yang CS, Brady JF, Hong JY Dietary effects on cytochromes P450, xenobiotic metabolism, and toxicity. FASEB J 1992 6 737. 

Sariaslani FS (1991) Microbial cytochromes P-450 and xenobiotic metabolism. Adv Appl Microbiol 36 133-177. 

Hakkola, J., Pasanen, M., Purkunen, R., Saarikoski, S., Pelkonen, O., Maenpaa, J., Rane, A. and Raunio, H. (1994) Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochemical Pharmacology, 48 (1), 59-64. 

Hepatic mixed-function oxidase activities demonstrated seasonal trends, with higher specific activities in the cold weather months in both populations with few differences in enzyme activities or cytochrome levels between the two populations. Metabolism of aldrin, dieldrin and DDT was similar between the two populations. R fish have larger relative liver size and, therefore, a greater potential for xenobiotic metabolism. However, biotransformation appears to be of minor importance in chlorinated alicyclic insecticide resistance in mosquitofish barriers to penetration appear to be of greater importance and an implied target site insensitivity appears to be the most important factor in resistance. 

L. W. Wormhoudt, J. N. Commandeur, N. P. Vermeulen, Genetic Polymorphisms of Human V-Acetyltransferase, Cytochrome P450, Glutathione 5-Transferase, and Epoxide Hydrolase Enzymes Relevance to Xenobiotic Metabolism and Toxicity , Crit. Rev. Toxicol. 1999, 29, 59 - 124. 

A striking feature of the collection of human brain cytochrome P450s discussed in the present review is the obvious major classes they fall into. With the exception of CYP26A1, which appears to be alone in the retinoic acid metabolic pathway, all the other brain P450s, including those normally considered xenobiotic-metabolizing, are either involved in the metabolism (or synthesis, in the case of CYP51, the... 

Bhagwat SV, Boyd MR, Ravindranath V. 1995a. Brain mitochondrial cytochromes P450 xenobiotic metabolism, presence of multiple forms and their selective inducibility. Arch Biochem Biophys 320 73-83. 

Johri A, Dhawan A, Lakhan Singh R, Parmar D. 2006. Effect of prenatal exposure of deltamethrin on the ontogeny of xenobiotic metabolizing cytochrome P450s in the brain and liver of offsprings. Toxicol Appl Pharmacol 214 ... 

Lewis, D. F. V. (1999) Homology modelling of human cytochromes P450 involved in xenobiotic metabolism and rationalization of substrate selectivity. Exp. Toxicol. Pathol. 51, 369-374. 

Carlson, G.P. Day, B.J. (1992) Induction by pyridine of cytochrome P450IIE1 and xenobiotic metabolism in rat lung and liver. Pharmacology, 44, 117-123... 

The lowest dose effects of diuron are seen at 0.27 mg kg-1 per day. Almost all of the low-dose expression changes are related to genes involved with xenobiotic metabolism and transport, including cytochrome P450 enzymes and several transferases. These data indicate that the cells are responding appropriately to a potentially toxic xenobiotic. These effects are widespread across the set of chemicals tested in ToxCast, so it is of interest that 2,4-D does not trigger a similar xenobiotic metabolism response. 

The ability of PBBs to induce hepatic Phase I xenobiotic metabolizing enzymes (cytochrome P-450-dependent monooxygenases) is well documented (Dannan et al. 1978b, 1982a, 1982b, 1983 Ecobichon et al. 1979 Moore et al. 1978, 1979 Parkinson et al. 1983 Robertson et al. 1982 Schramm et al. 1985). PBB mixtures were classified as "mixed-type" inducers of hepatic microsomal monooxygenases and... 

The cytochrome P450 system is the principal enzyme system for the metabolism of lipophilic xenobiotics. It is a heme-containing, membrane-bound, multi-enzyme system which is present in many tissues in vivo but is present at the highest level in liver. A coenzyme, cytochrome P450 NADPH oxidoreductase (OR), is essential for P450 catalytic function and cytochrome bs may stimulate catalytic activities of some enzymes. In human liver, it is estimated that there are 15-20 different xenobiotic-metabolizing cytochrome P450 forms. A standard nomenclature, based on relatedness of the amino acid sequences, has been developed (Nelson et al., 1993). The most recent... 

In vitro systems containing human xenobiotic-metabolizing enzymes can provide qualitative data, such as the human metabolites which may be produced in vivo and which enzymes are capable of producing these metabolites. When comparing quantitative aspects of metabolism among different cytochrome P450 forms in a cDNA expression system, the data can be interpreted in two contexts ... 

The field of xenobiotic metabolism is rich with a myriad of different, often competing, pathways of metabolism. Efforts at cDNA expression have only begun to develop comprehensive systems for the analysis of all Phase I and all Phase II enzymes. A comprehensive set of human cytochrome P450 and Phase II enzymes is not available in the context of a single host cell type, but given the rate of progress, we can look forward to nearly complete systems in the near future. 

It should be noted that this is not an exhaustive list and that in different species, different numbers of isozymes exist. It serves solely to illustrate the multiplicity of the forms of cytochrome P-450 generally involved with xenobiotic metabolism and the differences and similarities between them. 

There are five forms of the enzyme, but only two, the microsomal and soluble forms are important in xenobiotic metabolism. These two forms have different substrate specificities. The microsomal form is located in the endoplasmic reticulum in close proximity to cytochromes P-450, and like the latter is also present in greater amounts in the centrilobular... 

The level of a particular enzyme involved in xenobiotic metabolism can obviously affect the extent of metabolism by that enzyme. Again, competition may play a part if endogenous and exogenous substrates are both metabolized by an enzyme, as is the case with some of the forms of cytochromes P-450, which metabolize steroids, or NADPH cytochrome P-450 reductase and cytochrome b5 reductase, which are also involved in heme catabolism and fatty acid metabolism, respectively. 

Ding X, Kaminsky LS. Human extrahepatic cytochromes P450 function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol 2003 43 149-173. 

Inhibitory antibodies are frequently used in studies of xenobiotic metabolism, usually to estimate the contribution of particular enzymes in multienzyme mixtures. An important example is the use of antibodies to estimate the contribution of individual cytochrome P450 isoforms to the overall metabolism of a xenobiotic in microsomal preparations. 

Whereas most, if not all, of the enzymes involved in xenobiotic metabolism can form reactive metabolites (Table 8.1), the enzyme systems most frequently involved in the activation of xenobiotics are those which catalyze oxidation reactions. The cytochrome P450 monooxygenases (CYP) are by far the most important enzymes involved in the oxidation of xenobiotics. This is because of the abundance of CYP (especially in the liver), the numerous isozymes of CYP, and the ability of CYP to be induced by xenobiotic compounds. 

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