Cytochrome P450 multiplicity

Fasco, M.J., L.J. Piper, and L.S. Kaminsky (1979). Cumene hydroperoxide-supported microsomal hydroxylations of warfarin—A probe of cytochrome P450 multiplicity and specificity. Biochem. Pharmacol. 28, 97 103. 

CHOE, S., DILKES, B.P., FUJIOKA, S., TAKATSUTO, S., SAKURAI, A., FELDMANN, K.A., The DWF4 gene of Arabidopsis encodes a cytochrome P450 that mediates multiple 22-hydroxylation steps in brassinosteroid biosynthesis, Plant Cell, 1998,10, 231-243. 

Weaver, R. et al. 2003. Cytochrome P450 inhibition using recombinant proteins and mass spectrom-etry/multiple reaction monitoring technology in a cassette incubation. Drug Metab. Dispos. 31 955. 

Dabrowski, M.J., Schrag, M.L., Wienkers, L.C. and Atkins, W.M. (2002) Pyrene-pyrene complexes at the active site of cytochrome P450 3 A4 evidence for a multiple substrate binding site. Journal of the American Chemical Society, 124 (40), 11866-11867. 

Korzekwa, K.R., Krishnamachary, N., Shou, M., Ogai, A., Parise, R.A., Rettie, A.E., Gonzalez, F.J. and Tracy, T.S. (1998) Evaluation of atypical cytochrome P450 kinetics with two-substrate models evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites. Biochemistry, 37 (12), 4137-4147. 

Other docking algorithms such as Glide [33], Dock [34] and GOLD [35] have also been used to predict the site of metabolism, and a recent study compared the performance of multiple algorithms in the field of cytochrome P450s [36],... 

Wester, M.R., Johnson, E.F., Marques-Soares, C., Dansette, P.M., Mansuy, D. and Stout, C.D. (2003) Structure of a substrate complex of mammalian cytochrome P450 2C 5 at 2.3 A resolution evidence for multiple substrate binding modes. Biochemistry, 42, 6370-6379. 

Anandatheerthavarada HK, Addya S, Dwivedi RS, Biswas G, Mullick J, et al. 1997. Localization of multiple forms of inducible cytochromes P450 in rat liver mitochondria immunological characteristics and patterns of xeno-biotic substrate metabolism. Arch Biochem Biophys 339 136-150. 

Bhagwat SV, Boyd MR, Ravindranath V. 1995a. Brain mitochondrial cytochromes P450 xenobiotic metabolism, presence of multiple forms and their selective inducibility. Arch Biochem Biophys 320 73-83. 

Bhamre S, Anandatheerathavarada HK, Shankar SK, Boyd MR, Ravindranath V. 1993. Purification of multiple forms of cytochrome P450 from a human brain and reconstitution of catalytic activities. Arch Biochem Biophys 301 251-255. 

Fig. 2. Schematic representation of paclitaxel biosynthesis. Dimethylallyl-diphosphate and isopentenyl-diphosphate are condensed through geranylgeranyl diphosphate synthase activity to render geranylgeranyl-diphosphate (GGPP). GGPP is converted into taxa-4(5), 11 (12)-diene in a reaction catalyzed by the taxane synthase (TS). A series of reactions catalyzed by cytochrome P450 monoxygenases lead to the production of a taxane intermediate that is further converted to baccatin III through enzymes-driven oxidation and oxetane ring formation. The side chain moiety of paclitaxel is derived from L-phenylalanine. Three consecutive arrows mean multiple steps. Ac, acetyl Bz, benzoyl.

Metabolism - Unchanged nelfinavir comprised 82% to 86% of the total plasma. In vitro multiple cytochrome P450 isoforms including CYP3A and CYP2C19 are responsible for metabolism of nelfinavir. One major and several minor oxidative... 

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