Mono-oxygenase, cytochrome

Cytochrome P450 (CYP) Cytochrome P450 isozymes Cytochrome P450 mono-oxygenases Mixed function oxidases... 

Cytochrome P450 (CYP) mono-oxygenases, also called mixed function oxidases, are versatile hemoprotein enzymes that catalyze the cleavage of molecular oxygen to incoiporate one oxygen atom into a substrate molecule and one atom into water [1]. The general stoichiometry of the reaction is as follows (S-H, substrate) ... 

P450 Mono-oxygenase System. Table 1 Overview of the cytochrome P450 superfamily in humans... 

FIG. 21 Schematic diagram of cytochrome P450 mono-oxygenase reaction with substrate RH and product ROH. 

The major mono oxygenases in the endoplasmic reticulum are cytochrome P450s—so named because the enzyme was discovered when it was noted that preparations of microsomes that had been chemically reduced and then exposed to carbon monoxide exhibited a distinct peak at 450 nm. Among reasons that this enzyme is important is the fact that approximately 50% of the drugs humans ingest are metabolized by isoforms of cytochrome P450 these enzymes also act on various carcinogens and pollutants. 

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... 

Cytochrome P450s work by activating molecular oxygen (O2). They are all classified as mono-oxygenases because in the overall catalytic process, O2 is split into two oxygen atoms but only one atom is utilized in oxidizing the substrate (RH) while the second atom is reduced by two electrons to form water [Eq. (4.1)]. 

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). 

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

The formation of the monodehydroascorbate free radical by dopamine P-mono-oxygenase was similarly demonstrated by the acceleration of the reduction of Fe(III)-cytochrome c and by direct spectrophotometry at 360 nm The action of the laccase from the mushroom Agaricus hisporum on catechol yielded also the semiquinone as the result of a one-electron transfer... 

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,... 

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. 

Pisatin (6.23) is an isoflavonoid phytoalexin that is synthesized by pea (Pisum sativum L.) as a response to infection (Preisig et al., 1989). Subsequently, it was shown that pathogens capable of demethylating pisatin were tolerant of this phytoalexin. The enzyme responsible for demethylation is a specific cytochrome P450 mono-oxygenase released by the fungus Nectria haematococca (Delserone et al., 1999). 

The oxidative cyclization of an ortho-hydroxy-methoxy-substituted aromatic system giving a methylenedioxy group is also known to involve a cytochrome P-450-dependent mono-oxygenase. This enzyme hydroxylates the methyl to yield a formaldehyde hemiacetal intermediate, which can cyclize to the methylenedioxy bridge (the acetal of formaldehyde) by an ionic mechanism (Figure 2.21). 

Cytochrome P-450 enzymes have been isolated from a variety of mammalian tissues, insects, plants, yeasts and bacteria. The P-450 cytochromes (Gunter and Turner, 1991) are membrane bound mono-oxygenase enzymes which catalyse oxygen atom transfer to entrapped non-polar substrates. The binding of carbon monoxide to the enzyme produces a split in the 420 nm Soret band to give bands at 364 and 450 nm. The absorption at 450 nm distinguishes the hemoprotein from all others and hence provides... 

PAULI, H.H., KUTCHAN, T.M., Molecular cloning and functional heterologous expression of two alleles encoding (5>Y-methylcoclaurine 3 -hydroxylase (CYP80B1), a new methyl jasmonate-inducible cytochrome P-450-dependent mono-oxygenase of benzylisoquinoline alkaloid biosynthesis. Plant J., 1998, 13, 793-801. 

MEIJER, A.H., CARDOSO, M.I.L., VOSKUILEN, J.T., DE WAAL, A., VERPOORTE, R., HOGE, J.H.C., Isolation and characterization of a cDNA clone from Catharanthus roseus encoding NADPH cytochrome P-450 reductase, an enzyme essential for reactions catalyzed by cytochrome P-450 mono-oxygenases in plants. Plant J., 1993,4,47-60. 

Matson, R. S., and Fulco, A. J. 1981. Hydroxystearates as Inhibitors of Palmitate Hydroxylation Catalyzed by the Cytochrome-P-450 Mono-Oxygenase from Bacillus megaterium. Biochem. Biophys. Res. Comm., 103, 531-535. 

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