Cytochrome P450 -dependent

Since endosulfan is a cytochrome P450-dependent monooxygenase inducer, the quantification of specific enzyme activities (e.g., aminopyrine-A -demethylase, aniline hydroxylase) may indicate that exposure to endosulfan has occurred (Agarwal et al. 1978). Because numerous chemicals and drugs found at hazardous waste sites and elsewhere also induce hepatic enzymes, these measurements are nonspecific and are not necessarily an indicator solely of endosulfan exposure. However, these enzyme levels can be useful indicators of exposure, together with the detection of endosulfan isomers or the sulfate metabolite in the tissues or excreta. 

Exposure. Known biomarkers of exposure to endosulfan include the measurement of endosulfan or its metabolites in tissue and excreta (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968) these measurements can indicate whether absorption of endosulfan has occurred. The presence of the parent compound and its metabolites are specific biomarkers for endosulfan exposure. However, no studies are available that quantify the concentrations of endosulfan or its metabolites in relation to specific environmental exposure levels. Since endosulfan induces cytochrome P450-dependent monooxygenases... 

Boon, J.P., Van Arnhem, E., and Jansen, S. et al. (1992). The toxicokinetics of PCBs in marine mammals with special reference to possible interactions of individual congeners with cytochrome P450 dependent monooxygenase systems an overview. In C.H Walker and D. Livingstone (1992). Persistent Pollutants in Marine Ecosystems 119-160. 

Analysis of reaction mixtures for 1-propanol and 2-propanol following incubation of NDPA with various rat liver fractions in the presence of an NADPH-generating system is shown in Table I ( ). Presence of microsomes leads to production of both alcohols, but there was no propanol formed with either the soluble enzyme fraction or with microsomes incubated with SKF-525A (an inhibitor of cytochrome P450-dependent oxidations). The combined yield of propanols from 280 ymoles of NDPA was 6.1 ymoles and 28.5 ymoles for the microsomal pellet and the 9000 g supernatant respectively. The difference in the ratio of 1- to 2-propanol in the two rat liver fractions may be due to differences in the chemical composition of the reaction mixtures (2) Subsequent experiments have shown that these ratios are quite reproducible. For comparison, Table I also shows formation of propanols following base catalyzed decomposition of N-propyl-N-nitrosourea. As expected (10,11), both propanol isomers were formed, the total yield in this case being almost quantitative. 

Dufosse, L. and de Echanove, C., The last step in the biosynthesis of aryl carotenoids in the cheese ripening bacteria Brevibacterium linens ATCC 9175 (Brevibacterium aurantiacum sp. nov.) involves a cytochrome P450-dependent monooxygenase. Food Res. Int, 38, 967, 2005. 

Humphreys, J. M. Hemm, M. R. Chappie, C. Ferulate 5-hydroxylase fromArahidopsis is a multifunctional cytochrome P450-dependent monooxygenase catalyzing parallel hydroxylations in phenylpropanoid metabolism. Proc. Natl. Acad Sci. USA 1999, 96, 10045-10050. 

Chappie, C. (1998) Molecular-genetic analysis of plant cytochrome P450-dependent monooxygenases. Annual Review of Plant Physiology and Plant Molecular Biology, 49, 311-343. 

Johnson, W.T. and T.B. Smith. 1994. Copper deficiency increases cytochrome P450-dependent 7-ethoxy-resorufin-O-deethylase activity in rat small intestine. Proc. Soc. Exper. Biol. Med. 207 302-308. 

Fouchecourt, M.O. and J.L. Riviere. 1995. Activities of cytochrome P450-dependent monooxygenases and antioxidant enzymes in different organs of Norway rats (Rattus norvegicus) inhabiting reference and contaminated sites. Chemosphere 3L4375A386. 

In microsomes from Sinapis alba L.,33,34 Tropaeolum majus L.,35,36 and Carica papaya L.,37 the aromatic amino acids (tyrosine and phenylalanine) have been shown to be converted to the corresponding oximes by cytochrome P450-dependent monooxygenases. The conversion of tyrosine to the corresponding oxime in microsomes from S. alba was approximately 1000 fold lower than in microsomes from the cyanogenic sorghum.33 This made a biochemical approach for the isolation... 

Pinto, A., Abraham, N. G., Mullane, K. M., Cytochrome P450-dependent monoxygenase activity and endothelial-dependent relaxations induced by arachidonic acid. J. Pharmucol. Exp. Ther. 236 (1986),... 

Jousserandot, A., Boucher, J. L., Henry, Y., Niklaus, B., Clement, B., Mansuy, D., Microsomal cytochrome P450 dependent oxidation of N-hydroxyguanidines, amidoximes, and ket oximes mechanism of the oxidative cleavage of their C=N(OH) bond with formation of nitrogen oxides, Biochemistry 37 (1998),... 

FIGURE 4.44 Cytochrome P450-dependent oxidative conversion of cholesterol to progesterone... 

Mansuy D, Valadon P, Erdelmeier I, et al. Thiophene S-oxides as new reactive metabolites formation by cytochrome P450 dependent oxidation and reaction with nucleophiles. J Am Chem Soc 1991 113(20) 7825—7826. 

Allosteric behavior in cytochrome p450-dependent in vitro drug-drug interactions a prospective based on conformational dynamics. Chemical Research in Toxicology, 14 (4), 338-347. 

Ingelman-Sundberg, M. (2001) Implications of polymorphic cytochrome p450-dependent drug metabolism for drug development. Drug Metabolism and Disposition, 29 (4 Pt 2), 570-573. 

Acetaminophen (4.108) is hepatotoxic at higher doses, a toxicity explained by a cytochrome P450 dependent activation to A-acetyl-p-benzoquinonimine, which binds covalently to critical proteins (Chapt. 7 in [21]). However, the role of the hydrolytic step in acetaminophen-induced nephrotoxicity is not entirely clear. Early studies suggested a deacetylase-dependent activation of... 

Another mechanism of dearylation has been proven for tris(2-methylphen-yl) phosphate, and it is a pathway whose first step must be cytochrome P450 dependent. As shown in Fig. 9.10, the compound is hydroxylated at a Me group to yield the hydroxymethyl analogue 9.46. The latter then breaks down by intramolecular nucleophilic attack to form 2-(2-methylphenoxy)-4//-l,3,2A5-benzodioxaphosphinin-2-one (9.47, Fig. 9.10). This reaction of cy-clization occurs with loss of a ortho-cresyl moiety and is catalyzed by serum albumin [102], The cyclized product is a more potent inhibitor of esterases than tris(2-methylphenyl) phosphate, and it is also more toxic [100][101],... 

M. Delaforge, A. Piffeteau, J. L. Boucher, A. Viger, Nitric Oxide Formation During the Cytochrome P450-Dependent Reductive Metabolism of 18-Nitro-Oxyandrostenedione , J. Pharmacol. Exp. Ther. 1995, 274, 634 - 640. 

Minn AT, Pelczar H, Denizot C, Martinet M, Heydel JM, et al. 2005. Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa. Drug Metab Dispos 33 1229-1237. 

A. Cytochrome P450-dependent mono oxygenases reactions 3... 

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