Microsomes cytochrome

Evidence suggests that endosulfan can induce microsomal enzyme activity. Increased liver microsomal cytochrome P-450 activity was observed in male and female rats after single and multiple administrations of endosulfan (Siddiqui et al. 1987a Tyagi et al. 1984). Increased enzyme activity was observed in hepatic and extrahepatic tissues. Based on the increase in aminopyrine-A-demethylase and aniline hydroxylase activity, endosulfan has been shown to be a nonspecific inducer of drug metabolism (Agarwal et al. 1978). 

Under anaerobic conditions, p,p -DDT is converted to p,p -DDD by reductive dechlorination, a biotransfonnation that occurs postmortem in vertebrate tissues such as liver and muscle and in certain anaerobic microorganisms (Walker and Jefferies 1978). Reductive dechlorination is carried out by reduced iron porphyrins. It is carried out by cytochrome P450 of vertebrate liver microsomes when supplied with NADPH in the absence of oxygen (Walker 1969 Walker and Jefferies 1978). Reductive dechlorination by hepatic microsomal cytochrome P450 can account for the relatively rapid conversion of p,p -DDT to p,p -DDD in avian liver immediately after death, and mirrors the reductive dechlorination of other organochlorine substrates (e.g., CCI4 and halothane) under anaerobic conditions. It is uncertain to what extent, if at all, the reductive dechlorination of DDT occurs in vivo in vertebrates (Walker 1974). 

Lewis DFV. Qn the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics. Biochem Pharmacol 2000 60 293-306. 

Cosme J, Johnson EF. Engineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding. /FtoZ Chem 2000 275 2545-53. 

Williams PA, Cosme J, Sridhar V, Johnson EF, McRee DE. Mammalian microsomal cytochrome P450 monooxygenase structural adaptations for membrane binding and functional diversity. Mol Cell 2000 5 121-31. 

Yano JK, Wester MR, Schoch GA, Griffin KJ, Stout CD, Johnson EF. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution. J Biol Chem 2004 279 38091-4. 

Figure 11-6. Cytochrome P450 hydroxylase cycle in microsomes. The system shown is typical of steroid hydroxylases of the adrenal cortex. Liver microsomal cytochrome P450 hydroxylase does not require the iron-sulfur protein FejSj. Carbon monoxide (CO) inhibits the indicated step.

Costa AK, Katz ID, Ivanetich KM. 1980. Trichloroethylene Its interaction with hepatic microsomal cytochrome P-450 in vitro. Biochem Pharmacol 29 433-439. 

Miller RE, Guengerich FP. 1982. Oxidation of trichloroethylene by liver microsomal cytochrome P-450 Evidence for chlorine migration in a transition state not involving trichloroethylene oxide. Biochemistry 21 1090-1097. 

Capdevila, J.A., Yadagiri, P., Manna, S. and Falck, J.R. (1986). Absolute configuration of the hydroxyeicosatetraenoic acids (HETEs) formed during catalytic oxygenation of arachidonic acid by microsomal cytochrome P-450. Biochem. Biophys. Res. Commun. 141, 1007-1011. 

Hereditary methemoglobinemia is classified into three types a red blood cell type (type I), a generalized type (type II), and a blood cell type (type HI). Enzyme deficiency of type I is limited to red blood cells, and these patients show only the diffuse, persistent, slate-gray cyanosis not associated with cardiac or pulmonary disease. In type II, the enzyme deficiency occurs in all cells, and patients of this type have a severe neurological disorder with mental retardation that predisposes them to early death. Patients with type III show symptoms similar to those of patients with type I. The precise nature of type III is not clear, but decreased enzyme activity is observed in all cells (M9). It is considered that uncomplicated hereditary methemoglobinemia without neurological involvement arises from a defect limited to the soluble cytochrome b5 reductase and that a combined deficiency of both the cytosolic and the microsomal cytochrome b5 reductase occurs in subjects with mental retardation. Up to now, three missense mutations in type I and three missense mutations, two nonsense mutations, two in-frame 3-bp deletions, and one splicing mutation in type n have been identified (M3, M8, M31). 

Yamazaki, S., Sato, K., Suhara, K. et al. (1993) Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Journal of Biochemistry, 114 (5), 652-657. 

Parkinson, A., Thomas, P.E., Ryan, D.E. etal. (1983) Differential time course of induction of rat liver microsomal cytochrome P 450 isozymes and epoxide hydrolase by Aroclor 1254. Archives of Biochemistry and Biophysics, 225, 203-215. 

Hubl, U. and Stevenson, D.E. (2001) In vitro enzymic synthesis of mammalian liver xenobiotic metabolites catalyzed by ovine liver microsomal cytochrome P450. Enzyme and Microbial Technology, 29, 306-311. 

Guengerich FP. Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem Res Toxicol 1990 3[4] 363 371. 

Superoxide generation was detected via the NADPH-dependent SOD-inhibitable epinephrine oxidation and spin trapping [15,16], Grover and Piette [17] proposed that superoxide is produced equally by both FAD and FMN of cytochrome P-450 reductase. However, from comparison of the reduction potentials of FAD (-328 mV) and FMN (190 mV) one might expect FAD to be the most efficient superoxide producer. Recently, the importance of the microsomal cytochrome h558 reductase-catalyzed superoxide production has been shown in bovine cardiac myocytes [18]. 

Iron complexes or microsomal nonheme iron are undoubtedly obligatory components in the microsomal oxidation of many organic compounds mediated by hydroxyl radicals. In 1980, Cohen and Cederbaum [27] suggested that rat liver microsomes oxidized ethanol, methional, 2-keto-4-thiomethylbutyric acid, and dimethylsulfoxide via hydrogen atom abstraction by hydroxyl radicals. Then, Ingelman-Sundberg and Ekstrom [28] assumed that the hydroxylation of aniline by reconstituted microsomal cytochrome P-450 system is mediated by hydroxyl radicals formed in the superoxide-driven Fenton reaction. Similar conclusion has been made for the explanation of inhibitory effects of pyrazole and 4-methylpyrazole on the microsomal oxidation of ethanol and DMSO [29],... 

Interactive effects of PCBs on the induction of rat (Rattus sp.) liver microsomal cytochrome P-450c... 

Shimada, T. and Y. Sawabe. 1983. Activation of 3,4,3, 4 -tetrachlorobiphenyl to protein-based metabolites by rat liver microsomal cytochrome P-448 containing monooxygenase system. Toxicol. Appl. Pharmacol. 70 486-493. 

Rodrigues, A.D. et al. 1994. Measurement of liver microsomal cytochrome p450 (C YP2D6) activity using [0-methyl-14C]dextromethorphan. Anal. Biochem. 219 309. 

Nastainczyk W, Ahr H, Ulrich V, et al. 1982a. The mechanism of the reductive dehalogenation of polyhalogenated compounds by microsomal cytochrome P450. 799-808. 

Nastainczyk W, Ahr HJ, Ullrich V. 1982b. The reductive metabolism of halogenated alkanes by liver microsomal cytochrome P450. Biochem Pharmacol 31 391-396. 

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),... 

Abou-Donia MB, Lapadula DM, Campbell G, et al. 1985 The synergism of n-hexane-induced neurotoxicity by methyl isobutyl ketone following subchronic (90 days) inhalation in hens Induction of hepatic microsomal cytochrome P-450. Toxicol Appl Pharmacol 81(1) 1-16. 

Toftgard R, Haaparanta T, Eng L, etal. 1986. Rat lung and liver microsomal cytochrome P-450 isozymes involved in the hydroxylation of M-hexane. Biochem Pharmacol 35(21) 3733-3738. 

Gorsky LD, Koop DR, Coon MJ. On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J Biol Chem 1984 259(11) 6812-6817. 

Groves JT, McClusky GA. Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate. Biochem Biophys Res Commun... 

Bowry VW, Ingold KU. A radical clock investigation of microsomal cytochrome-P-450 hydroxylation of hydrocarbons—rate of oxygen rebound. J Am Chem Soc 1991 113(15) 5699-5707. 

Mathews JM, Bend JR. N-alkylaminobenzotriazoles as isozyme-selective suicide inhibitors of rabbit pulmonary microsomal cytochrome P-450. Mol Pharmacol 1986 30(l) 25-32. 

Hayes JR, Hartgrove RW, Hundley SG, et al. 1975. Interaction of endrin and dieldrin with hepatic microsomal cytochrome 450 from the rat, mouse, and endrin-susceptible and resistant pine voles. Toxicol Appl Pharmacol 32 559-565. 

Characterization of human microsomal cytochrome P-450 enzymes. Annual Review of Pharmacology and Toxicology, 29, 241-264. 

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