P450-monooxygenases

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer.

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. 

Estrogens are formed by the aromatization of androgens in a complex process that involves three hydroxyla-tion steps, each of which requires O2 and NADPH. The aromatase enzyme complex is thought to include a P450 monooxygenase. Estradiol is formed if the substrate of this enzyme complex is testosterone, whereas estrone results from the aromatization of androstenedione. 

This can be degraded by several mycobacteria including Mycobacterium aurum strain MOl (Combourieu et al. 1998), Mycobacterium strain RPl (Poupin et al. 1998), and Mycobacterium chelonae (Swain et al. 1991). The reaction is initiated by a cytochrome P450 monooxygenase that is also active against pyrrolidine and piperidine (Poupin et al. 1998). 

Circulating melatonin is metabolized mainly in the liver, where it is first hydroxylated in the C6-position by cytochrome P450 monooxygenases (isoenzymes... 

Cashman, J.R. (2005) Some distinctions between flavin-containing and cytochrome P450 monooxygenases. Biochemical and Biophysical Research Communications, 338, 599-604. 

Cytochrome P450 monooxygenases (P450s) have significant potential in biotransformation applications because their ability to insert molecular oxygen regiospecifically and... 

Urlacher, V.B. and Eiben, S. (2006) Cytochrome P450 monooxygenases perspectives for synthetic application. 

Fig. 22.3 Cytochrome P450 monooxygenases and nicotine metabolism. An alignment of the amino acid sequences of the enzymes 2A6 and 2D6. Occurrences of the same amino acid residue at the same position are shown in black. Putative substrate recognition sites (SRS1—...

HU, a freely water-soluble molecule, crosses the intestinal wall and other cells by passive diffusion [5, 6], and tissue concentration of HU rapidly matches its blood concentration [7]. The oral bioavailability of HU is nearly complete and hence therapeutically simple to administrate. HU undergoes biotransformation and is converted into urea by a yet-to-be identified hepatic P450 monooxygenase (CYP) enzyme [8, 9], Elimination of HU and its metabolites involves both renal and non-renal mechanisms. 

M. Hara, S. Iazvovskaia, H. Ohkawa, Y. Asada, and J. Miyake, Immobilization of P450 monooxygenase and chloroplast for use in light-driven bioreactors. J. Biosci. Bioeng. 87, 793-797 (1999). 

SCHULER, M.A., Plant cytochrome P450 monooxygenases, Crit. Rev. in Plant Sci., 1996,15,235-284. 

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