Cytochrome P-450 oxygenase

Pretreatment of male mice with compounds that affect cytochrome P-450 oxygenases altered the toxicity of a single intraperitoneal injection of... 

These superoxo complexes are relevant models for the naturally occurring oxygen carriers hemoglobin and myoglobin, which contain ferroprotoporphyrin IX as an active center in which the sixth axial postion is occupied by the imidazole moiety of histidine.17 They also intervene as primary oxygen adducts in enzymatic cytochrome P-450 oxygenases.18... 

An axenic poplar cell culture experiment exhibited conclusively that poplar cells are capable of transforming and mineralizing TCE without the involvement of microbial metabolism. The metabolites of TCE in cell cultures include trichloroethanol, trichloroacetic acid, and dichloroacetic acid, which was the most predominant. Chloral hydrate was also found at levels lower than the detection limit and is a product of TCE oxidation by cytochrome P-450 oxygenase and the precursor of trichloroethanol and trichloroacetic acid in mammalian systems. The same metabolites were identified in field sites where vegetation was exposed to TCE contaminated groundwater and in laboratory studies. ... 

The first two carbinolamlnes named were synthesized using sequential catalysis by cytochrome P-450 oxygenase and glucuronyl transferase inmobllized from rabbit liver microsomes onto sepharose beads (64,65) as shown in scheme 3. 2-Pra1 idoxime chloride was allowed to decompose at pH 7.4 in the presence of immobilized UDP-glucuronyl transferase and the cofactor uridine... 

Cytochrome P-450 is frequently the oxygenase which detoxifies xenobiotics, including herbicides. Blocking the metaboHsm of a herbicide increases the activity or delays the inactivation, thus increasing the effectiveness of such herbicides as chlortoluron [15545-48-9] and bentazon [25057-89-0]... 

Cytochrome P-450 and other heme-containing oxygenases. J. T. Groves, Adv. Inorg. Biochem., 1979,1,119-145 (109). 

Andrae U. Evidence for the involvement of cytochrome P-450-dependent mono-oxygenase(s) in the formation of geno-toxic metabolites from N-hydroxyurea. Biochem Biophys Res Commun 1984 118 409-415. 

Cytochrome P-450. Cytochrome P-450 enzymes consist of a large number of haem-containing mono-oxygenases which catalyze aliphatic and aromatic hydroxylations, epoxidations, as well as other oxidation reactions thus, these enzymes are able to cleave aromatic C-H bonds and also... 

Tynes, R. and Hodgson, E. (1984). The measurement of FAD-containing oxygenase activity in microsomes containing cytochrome P-450.Xenobiotica 14 515-520. 

Hockin, L.J. and Paine, A.J. (1983). The role of 5-aminolevulinate synthetase, haem oxygenase and ligand formation in the mechanism of maintenance of cytochrome P-450 concentration in hepatocyte culture. Biochem. Pharmacol. 210 855-857. 

Cytochrome P-450 has been characterized in four stable states [Fe, Fe " RH, Fe RH, (O2—Fe ) RH (metastable)] during its oxygenase reaction cycle. In the complete native system a flavoprotein and a redoxin (putidaredoxin) act as electron donors but also as effectors that complement the cytochrome. In the more complex microsomal system the sequence and intermediates are less well defined the electron-transfer chain contains two flavoproteins and one cytochrome, whose interactions with cytochrome P-450 are still the subject of great controversy. 

Enzymatic hydroxylation of biological molecules is often catalyzed by hydroxylases. These types of enzymes are either oxygenases or peroxidases, in which the source of oxygen is O2 or H2O2, respectively. Cytochrome P-450-dependent enzymes represent a common class of enzymes that carry out hydroxylation reactions. L-Carnitine is a metabolite isolated from many organisms and its biosynthesis begins with the enzymatic hydroxylation of trimethyllysine. The intermediate, 3-hydroxyl-e-(A(A(ALtrimethyl)-L-lysine, is further... 

Natnre does not actually make a methylenedioxy group using formaldehyde. Instead, it modifies an existing ortAo-hydroxy-methoxy arrangement. Enzymic hydroxylation of the methoxy methyl converts this substitnent into what is identical to a hemiacetal of formaldehyde, and then acetal formation follows in a process analogous to a chemical synthesis. The hydroxylating enzyme involved is a cytochrome P-450 mono-oxygenase (see Box 11.4). 

The following is review on the molecular and physical properties of this class of monooxygenases, which are also known as hydroxylases. A typical monooxygenase reaction is the hydroxylation of an alkane to an alcohol which involves a reduced cosubstrate that reduces a second atom within the O2 molecule to form water. Flavin-containing monooxygenases include lysine oxygenase and 4-hydroxybenzoate hydroxylase. Reduced pteri-dines are involved in the phenylalanine hydroxylase and tryptophan hydroxylase reactions. See also Cytochrome P-450... 

In cellular smdies indium exposure has been associated with a general suppression of protein synthesis and the induction of heme oxygenase, which in turn is associated with the reduction of enzyme activities dependent on cytochrome P-450. The significance of these alterations in the synthesis and maintenance of various enzyme systems in relation to a possible carcinogenic response has not been determined. ... 

N-oxidation. The oxidation of nitrogen in tertiary amines, amides, imines, hydrazines, and heterocyclic rings may be catalyzed by microsomal enzymes or by other enzymes (see below). Thus the oxidation of trimethylamine to anN-oxide (Fig. 4.19) is catalyzed by the microsomal FAD-containing mono oxygenase. The N-oxide so formed may undergo enzyme-catalyzed decomposition to a secondary amine and aldehyde. This N to C transoxygenation is mediated by cytochromes P-450. The N-oxidation of 3-methylpyridine, however, is catalyzed by cytochromes P-450. This reaction may be involved in the toxicity of the analogue,... 

Reduced synthesis. The synthesis of enzymes may be decreased, resulting in a decrease in the in vivo activity. With cytochrome P-450 there are a number of ways in which this occurs. Thus, administration of the metal cobalt to animals will decrease levels of cytochromes P-450 by inhibiting both the synthesis and increasing the degradation of the enzyme. Thus, cobalt inhibits S-aminolaevulinic acid synthetase, the enzyme involved in heme synthesis. Cobalt will also increase the activity of heme oxygenase, which breaks down the heme portion to biliverdin. The compound 3-amino, 1, 2, 3-triazole decreases cytochromes P-450 levels by inhibiting porphyrin synthesis. 

Neims AH, Warner M, Loughnan PM, et al. Developmental aspects of the hepatic cytochrome P-450 mono-oxygenase system. Annu Rev Pharmacol Toxicol 1976 16 427. 

Unlike cytochrome P-450 reductase, NOS is a self-sufficient enzyme in that the oxygenation of its substrate, L-arginine, occurs at the heme-site in the N-terminal portion, termed the oxygenase domain, of the protein. Stoichiometric amounts of heme are present in NOS and are required for catalytic activity. 

Biological oxidation of sulfides involves cytochromes P-450 or flavin-dependent oxygenases. A chiral flavin model was prepared by Shinkai etal. and used as the catalyst in the oxidation of aryl methyl sulfides [87]. Flavinophane 30 (Scheme 6C.10) is a compound with planar chirality. It catalyzes the oxidation of sulfides with 35% H202 in aqueous methanol at -20°C in the dark. 

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