Biotransformations cytochrome P450 expressed

JONDORF, W.R. (1981) Drug metabolism as evolutionary probes. Drug Metab. Rev., 12, 379. KATO, R. and YAMOZOE, Y. (1990) Sex-dependent regulation of cytochrome P450 expression. In Frontiers of Biotransformation, Vol. II, Principles, Mechanisms and Biological Consequences of Induction, edited by K.Ruckpaul and H.Rein (London Taylor Francis). 

Zhang QY, Raner G, Ding XX, et al. Characterization of the cytochrome P450 CYP2J4-expression in rat small intestine and role in retinoic acid biotransformation from retinal. Arch Biochem Biophys 1998 353 257-264. 

The specific cytochrome P450 isoforms that mediate the biotransformation of clobazam and of its metabolites N-desmethylclobazam and 4 -hydroxyclobazam have been identified using cDNA-expressed P450 and P450-specific chemical inhibitors in vitro (13). The results of this study showed that ... 

The superfamily of P450 cytochrome enzymes is one of the most sophisticated catalysts of drug biotransformation reactions. It represents up to 25% of the total microsomal proteins, and over 50 cytochromes P450 are expressed by human beings. Cytochromes P450 catalyze a ivide variety of oxidative and reductive reactions, and react with chemically diverse substrates. Despite the large amount of information on the functional role of these enzymes combined with the knowledge of their three-dimensional structure, elucidation of cytochrome inhibition, induction, isoform selectivity, rate and position of metabolism all still remain incomplete [6]. 

Humans are exposed continuously and unavoidably to a myriad of potentially toxic chemicals that are inherently lipophilic and, consequently, very difficult to excrete. To effect their elimination, the human body has developed appropriate enzyme systems that can transform metabolically these chemicals to hydrophilic, readily excretable, metabolites. This biotransformation process occurs in two distinct phases. Phase I and Phase II, and involves several enzyme systems, the most important being the cytochromes P450. The expression of these enzyme systems is regulated genetically but can be modulated also other factors, such as exposure to chemicals that can either increase or impair activity. Paradoxically, the same xenobiotic-metabolizing enzyme systems also can convert biologically inactive chemicals to highly reactive intermediates that interact with vital cellular macromolecules and elicit various forms of toxicity. Thus, xenobiotic metabolism does not always lead to deactivation but can result also in metabolic activation with deleterious consequences. 

Cytochrome P450 (CYP) enzymes, particularly those in the CYP1, CYP2, and CYP3 gene families (1), catalyze the biotransformation of a wide variety of xenobiotic compounds. The organ that expresses the highest levels of CYP is the liver,... 

C. Kudla, Y. Keita et al. (1992). Biotransformation of caffeine and theophylline in mammalian cell lines genetically engineered for expression of single cytochrome P450 isoforms. Biochem. Pharmacol. 43, 225-235. 

A more complicated yet extremely enlightening example of the consequence of redox conditions on the ultimate expression of toxic outcomes is the mechanism of biotransformation through the oxidative family of enzymes know as the cytochrome P450 (GYP) superfamily. This enzyme system is responsible for an enormous array of biotransformations for substances that represent an extremely diverse range of molecular classes. 

Fujii T, Fujii Y, Machida K, Ochiai A, Ito M (2009) Efficient biotransformations using Escherichia coli with tolC acrAB mutations expressing cytochrome P450 genes. Biosci Biotechnol Biochem 73 805-810... 

Makaji, E. Trambitas, C. S. Shen, P. Holloway, A. C. Crankshaw, D. J. Effects of cytochrome P450 inhibitors on the biotransformation of fluorogenic substrates by adult male rat liver microsomes and cDNA-expressed rat cytochrome P450 isoforms. Toxicol. Set 2010,113, 293-304. 

---