Cytochrome P450 oxygenase

Scheme 10.6 Byproducts of cytochrome P450 oxygenase catalyzed epoxidation. Top N-alkylation of the porphyrin ring. Bottom group migration to give aldehydes. 

It is thought that phenytoin, - carbamazepine and phenobarbital increase the metabolism of the ciclosporin by the liver (hepatic cytochrome P450 oxygenase system) thereby decreasing the serum levels. Oxcarbazepine produced only small reductions in ciclosporin levels, and the effect is probably due to weak induction of the cytochrome P450 isoenzyme CTT3A. Phenytoin also possibly reduces the absorption of the ciclosporin. ... 

Figure 5.46 Proposed mechanism for C—S bond formation mediated by a mnltifnnctional cytochrome P450 oxygenase, setting the stage for heterocychzation and the minimal set of enzymes required for in vitro biosynthesis of camalexin.

In the same paper, the authors reported that incubation of Trp, Cys, and NADPH with the three cytochrome P450 oxygenases CYP79B2, CYP71B15, CYP71A12, and reductase partner produced camalexin, demonstrating that the set of these three enzymes is necessary and sufficient to synthesize this key Arabidopsis phytoa lexin [222],... 

Kaspera R, Croteau R (2006) Cytochrome P450 oxygenases of Taxol biosynthesis. Phytochem Rev 5 433 4... 

Ikezawa N, Iwasa K, Sato F (2009) CYP719A subfamily of cytochrome P450 oxygenases and isoquinoline alkaloid biosynthesis in Eschscholzia caltfomica. Plant Cell Rep 28 123-133... 

Phase I reactions include oxidation, reduction, hydrolysis, epoxide hydration, and dehydrohalogenation reactions. The cytochrome P450 oxygenase system (CYP450) is the most important one in the metabolism of foreign chemicals. These enzymes that oxidize xenobiotics are widely distributed in the body. They are found in high... 

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. 

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)]. 

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