Cytochrome P450 superfamily

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

Kelly SL, Lamb DC, Cannieux M, Greetham D, Jackson CJ, et al. 2001. An old activity in the cytochrome P450 superfamily (CYP51) and a new story of drugs and resistance. Biochem Soc Trans 29 122-128. 

Danielson, P. B. (2002) The cytochrome P450 superfamily biochemistry, evolution and dmg metabolism in humans. Curr. Drug. M. 3, 561-597. 

There are two basic types of sequence alignment. Single alignments compare pairs of sequences to find the best match and would be used to locate a DNA sequence on the genome. In contrast, multiple alignments compare sets of sequences with one another to identify overall similarities, and have been used to compare sequence similarity within a superfamily of proteins such as the cytochrome P450 superfamily (Fig. 1). 

MIZUTANI, M., WARD, E., OHTA, D., Cytochrome P450 superfamily in Arabidopsis thaliana isolation of cDNAs, differential expression and RFLP mapping of multiple cytochromes P450., Plant Mol. Biol., 1998, 37,39-52. 

Boddupalli, S. S., Hasemann, C. A., Ravichandran, K. G., Lu, J. Y., Goldsmith, E. J., Deisenhofer, J., and Peterson, J. A. 1992a. Crystallization and Preliminary-X-Ray Diffraction Analysis of P450terp and the Hemoprotein Domain of P450bm-3, Enzymes Belonging to 2 Distinct Classes of the Cytochrome P450 Superfamily. Proc. Nat.l Acad. Sci.,89, 5567-5571. 

It can therefore be seen that Hazardexpert is essentially a quantitative version of DEREK that is also able to take into account the important factors of metabolism and bioavailability. Both of the aforementioned programs, however, are more focused on the biological area of structure-toxicity evaluation, a factor they share with COMPACT. The latter is sufficiently different and specific relative to the previous methods to require some degree of introduction prior to a more descriptive treatment. As the COMPACT procedure developed out of research carried out on the cytochrome P450 superfamily of enzymes, it will be necessary to provide some biochemical background relating to these isozymes. 

Figure 4 Cytochrome P450 superfamily phylogenetic tree showing major gene families.

Munro AW, Girvan HM, McLean KJ. Variations on a (t)heme— novel mechanisms, redox partners and catalytic functions in the cytochrome P450 superfamily. Nat. Prod. Rep. 2007 24 585-609. 

Increase in urate levels during primate evolution Section 25.6.1 The cytochrome P450 superfamily Section 26.4.3... 

The initial and rate-limiting step of bile acid synthesis is oxidation of cholesterol to 7a-hydroxycholesterol by a mixed function oxidase from the cytochrome P450 superfamily, cholesterol 7a-hydroxylase (CYP7A1). 

A major organ of drag metaboUsm is the Hver, with a variety of DMEs impH-cated in the chemical alteration of drags and xenobiotics. This phase I metaboHsm of compounds frequently results in alterations such that the compounds are more rapidly eliminated from the body, and/or become ineffective or toxic. Oxidations mediated by enzymes of the GYP (cytochrome P450) superfamily account for a major proportion of these alterations. Thus, there is an urgent need to identify which compounds may interact with cytochrome P450s (as substrates) or which compounds may be (adversely) affected through induction/inhibition of cytochrome enzymatic activity. 

Jackson, C.J., D.C. Lamb, T.H. Marczylo, A.G. Warrilow, N.J. Manning, D.J. Lowe et al. (2002). A novel sterol 14alpha-demethylase/ferredoxin fusion protein (MCCYP51FX) from Methylo-coccus capsulatus represents a new class of the cytochrome P450 superfamily. J. Biol. Chem. 277, 46959 6965. 

Attar, R.M., E. Grotewold, G.E. Taccioli, G.O. Aisemberg, H.N. Torres, and N.D. Judewicz (1989). A cycloheximide-inducible gene of Neurospora crassa belongs to the cytochrome P450 superfamily Nucleic Acids Res. 17, 7535-7536. 

Ethanol is also oxidized to acetaldehyde in the liver by the microsomal ethanol oxidizing system, which comprises members of the cytochrome P450 superfamily of enzymes. Ethanol and NADPH both donate electrons in the reaction, which reduces O2 to 2H2O (Fig. 25.5). The cytochrome P450 enzymes all have two... 

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