Cytochrome P-450 monooxygenase system

Metabolism of BP mediated by the cytochrome P-450 monooxygenase system forms three classes of products phenols, dihydrodiols and quinones. Formation of phenols and dihydrodiols is obtained by an initial electrophilic attack of an enzyme-generated oxygen atom. 

Livingstone, D. R. Moore, M.N. Lowe, D.M. Casci, C. Farrar, S. 1985, Responses of the cytochrome P-450 monooxygenase system to diesel oil in the common mussel Mytilus edulis L. and the periwinkle, Littorina littorea L. Aquat. Toxicol. 1 79-91. 

Cytochromes P-450 MFO system. The majority of these reactions are catalyzed by one-enzyme system, the cytochromes P-450 monooxygenase system, which is located particularly... 

The cytochromes P-450 monooxygenase system is actually a collection of isoenzymes, all of which possess an iron protoporphyrin IX as the prosthetic group. The monomer of the enzyme has a molecular weight of 45,000 to 55,000. The enzyme is membrane bound within the endoplasmic reticulum. Cytochromes P-450 are closely associated with another vital component of the system, NADPH cytochrome P-450 reductase. This is a flavoprotein, which has 1 mol of FAD and 1 mol of FMN per mol of apoprotein. The monomeric molecular weight of the enzyme is 78,000. The enzyme transfers two electrons to cytochromes P-450, but one at a time. There only seems to be one reductase, which serves a group of isoenzymes of cytochromes P-450, and consequently, its concentration is 1/10 to 1/30 that of cytochromes P-450. 

Schenkman, J.B. and Kupfer, D., Eds., Hepatic Cytochrome P-450 Monooxygenase System, Pergamon Press, Oxford, 1982. 

Some Properties of a Self-Sufficient Cytochrome P-450 Monooxygenase System from Bacillus megaterium Strain ALA2... 

The catalytic role that the cytochrome P-450 monooxygenase system plays in the oxidation of xenobiotics is summarized in the cycle shown in Figure 4-1. - The initial... 

The cytochrome P-450 monooxygenase system. P-4503+ Cytochrome P-450 with heme iron in oxidized state (Fe3+) P-45021 cytochrome P-450 with iron in reduced state S substrate e electron. (Adapted from J. A. Trimbell, 1982. Principles of Biochemical Toxicology. Taylor Francis, London.)... 

Cytochrome P-450 monooxygenase system in the hepatic endoplasmic reticulum. P-450-Fe(III) = ferricytochrome P-450 P-450-Fe(II) = ferrocytochrome P-450 85 = cytochrome 85 Fpa = NADPH-cytochrome P-450 reductase Fpt, = NADH-cytochrome bj reductase XH = substrate. [Reproduced with permission from G. Mannering, K. W. Renton,... 

The majority of these reactions are catalysed by one enzyme system, the cytochromes P-450 monooxygenase system, which is located particularly in the SER of the cell. The enzyme system is isolated the so-called microsomal fraction which is formed from the endoplasmic reticulum when the cell is homogenized and fractionated by differential ultracentrifugation. Microsomal vesicles are thus fragments of the endoplasmic reticulum... 

As well as the cytochromes P-450 monooxygenase system there is also a system which involves FAD. This enzyme system is found particularly in the microsomal fraction of the liver and the monomer has a molecular weight of around 65 000. Each monomer has one molecule of FAD associated with it. The enzyme may accept electrons from either NADPH or NADH although the former is the preferred cofactor. It also requires molecular oxygen and the overall reaction is as written for cytochromes P-450 ... 

The metabolic formation of carbonyl sulfide from carbon disulfide was confirmed in an in vivo study (Dalvi and Neal 1978). After intraperitoneal injection of 14C-carbon disulfide in nonpretreated rats, carbonyl sulfide was excreted by the lung in greater quantities than carbon dioxide. Pretreatment with phenobarbital, however, resulted in a greater amount of excretion of carbon dioxide than carbonyl sulfide. In both experiments, excretion of 14C-carbonyl sulfide and carbon dioxide accounted for 14-43% of the total administered radioactivity, with about twice as much carbon dioxide. These results indicate that phenobarbital treatment caused induction of cytochrome P-450 which catalyzed the conversion of carbon disulfide to carbonyl sulfide faster in pretreated rats than in rats not pretreated with phenobarbital. The role of the cytochrome P-450 monooxygenase system in catalyzing carbonyl sulfide formation was also confirmed by in vitro studies (Dalvi et al. 1974, 1975). The rate of carbonyl sulfide formation was NADPH-dependent and increased with microsomes obtained from phenobarbital-treated rats. 

The nature of the hydroxylation reactions discussed above has been investigated. A hemA mutant defective in the biosynthesis of cytochromes was able to convert 2-octaprenyl-[ " C] phenol (50) to " C-labeled (J S, ruling out the involvement of the cytochrome P-450 monooxygenase system and suggesting the involvement of flavin-linked monooxygenases in these reactions. A mechanism analogous to that proposed for the flavin-... 

Nebert, D.W (1982). Genetic differences in the induction of monooxygenase activities by polycyclic aromatic compounds. In XB. Schenkman and D. Kupfer (eds). Hepatic Cytochrome P-450 Monooxygenase System. Pergamon Press, New York, NY, pp. 269-291. 

Satsmadjis J, Voutsinou-Taliadouri F (1983) Mytilus galloprovincialis and Parapenaeus longirostris as bioindicators of heavy metal and organochlorine pollution. Mar Biol 76 115-124 Schenkman JB, SligarSG, Cinti DL(1982) Substrate interaction with cytochrome P-450. In Schenkman JB, Kupfer D (eds) Hepatic cytochrome P-450 monooxygenase system. Pergamon Press, Oxford, pp 587-615... 

This section describes resolution of the cytochrome P 450 monooxygenase system of S. carbop/iitus, purification of the NADH-cytochrame P-450 reductase, and reconstitution of the hydroxylation activity by endogenous conqxinents (13). 

Cytochrome P-450 monooxygenase systems can be classified as of either two- or three-component type (43). Three-component-type systems are composed of cytochrome P-450 reductase, cytochrome P-450, and an iron-sulfur protein, whereas two-compo-nent-type systems are composed of cytochrome P-450 reductase and cytochrome P-450. Tlie results of many previous works have shown that almost all prokaryotes have three-component (mitochondrial) type cytochrome P-450 systems (29,45,46), and those of eukaryotes, such as yeast, are of the two-component (microsomal) type (47). Cytochrome... 

Serizawa N, Matsuoka T. A two component-type cytochrome P-450 monooxygenase system in a prokaryote that catalyzes hydroxyiation of ML-236B to pravastatin, a tissue-selective inhibitor of 3.hydroxy 3 methylgluiaryl coenzyme A reductase. Biochim Biophys Acta 1991 1084 35-40. 

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