Cytochrome P450 activity biotransformation

The level and activity of specific enzymes involved in biotransformation can differ depending on the species, strain, age, and sex of the test animal. For example, cats cannot carry out glucuronidation reactions, newborn rats have relatively low cytochrome P450 activity, and male rats are more sensitive to carbon tetrachloride toxicity than female rats. These differences are important to consider when interpreting the results from toxicological studies. The observation that age, sex, and genetics can significantly influence biotransformation reactions in animals raises the question of whether these characteristics also affect the biotransformation capacity of humans. 

Pharmacokinetics Hepatic cytochrome P450-mediated biotransformation of cyclophosphamide is needed for antitumor activity. One of the breakdown products is acrolein. 

A cytochrome P450 has been purified from Saccharomyces cerevisiae that has benzo[a]pyrene hydroxylase activity (King et al. 1984), and metabolizes benzo[fl]pyrene to 3- and 9-hydroxybenzo[fl]pyrene and benzo[fl]pyrene-7,8-dihydrodiol (Wiseman and Woods 1979). The transformation of PAHs by Candida Upolytica produced predominantly monohydroxyl-ated products naphth-l-ol from naphthalene, 4-hydroxybiphenyl from biphenyl and 3- and 9-hydroxybenzo[fl]pyrene from benzo[fl]pyrene (Cerniglia and Crow 1981). The transformation of phenanthrene was demonstrated in a number of yeasts isolated from littoral sediments and of these, Trichosporumpenicillatum was the most active. In contrast, biotransformation of benz[fl]anthracene by Candida krusei and Rhodotorula minuta was much slower (MacGillivray and Shiaris 1993). 

Relatively innocuous factors can also sometimes influence liver enzyme activity. For example, the metabolic elimination of the bronchodilator theophylline has been reported to be prolonged in patients with influenza A or adenovirus infections. In 1990, an influenza epidemic in Seattle resulted in the admission of 11 children with high serum levels of theophylline and confirmed drug toxicity. These effects appear to be confined to cytochrome P450-based drug biotransformation. They may be related to the generation of interferons as a result of these infections, which, presumably, are causally related to the inhibitory effect on hydroxylases and demethylases. 

The initial activation of compounds is catalysed by various enzymes, depending on the chemical structure of the compound in question. The cytochrome P450 monooxygenase complex (CYP) is the major biotransforming system. In vertebrates it is present in all the organs of the body and particularly abundant in the liver. 

PE-free callus from Polypodium vulgare was shown to biotransform ecdysone fo 20-hydroxyecdysone, which is the last step in the biosynthetic pathway of the main plant PE. This hydroxylation is catalysed by a cytochrome P450 enzyme which was subsequently purified from that source (Canals et al, 2005). In another study, Reixach et al. (1999) have shown that 25-deoxy-20-hydroxyecdysone was transformed efficiently in both tissues into 20-hydroxyecdysone, but no 25-deoxyecdysteroids such as pterosterone and inokosterone were formed. Likewise, incubation of 2-deoxyecdysone produced exclusively ecdysone and 20E, indicating a high 2-hydroxylase activity in both tissues. 

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