Xenobiotic oxidative metabolism

C Montesissa, P Anfossi, G Vant Klooster, M Mengelers. The use of cultured hepatocytes from goats and cattle to investigate xenobiotic oxidative metabolism. Veterinary Research Communications 20 449-460, 1996. 

Cytochrome P450s are iron-containing enzymes that function in steroid biosyntheses and xenobiotic oxidative metabolism. P450cam is a water-soluble P450 isolated from the bacterium Pseudomonas putida that catalyzes the hy-droxylation of camphor. P450cam was the first member of this family to have its crystal structure solved. 

Phenols also constitute a major source of xenobiotic exposure to the body in the form of drugs and environmental pollutants. Oxidative metabolism of these compounds can lead to physiological damage, therefore the metabolism of these compounds is of great interest. LCEC has been a powerful tool for investigating the metabolism of aromatic compounds by the cytochrome P-450 system LCEC... 

Roberts ES, Vaz AD, Coon MJ. Catalysis by cytochrome P-450 of an oxidative reaction in xenobiotic aldehyde metabolism deformylation with olefin formation. Proc Natl Acad Sci USA 1991 88(20) 8963-8966. 

Quinones and other xenobiotics are metabolized primarily in the liver, and the end products are water-soluble compoimds that are excreted from the body. The first step in metabolism is usually an oxidative process (phase I detoxification), after which further oxidation and conjugation can occur (phase II detoxification). Although those reactions normally yield easily excreted products, some steps in the metabolic pathway may generate metabolites that are more toxic than the parent comporuid. 

Fig. 3.2 Biological abstraction. Yeast cells reflect anaerobic, reductive metabolism (intestine) as well as aerobic, oxidative metabolism (liver), if glycolysis is regarded as the most active pathway. Therefore, the yeast Saccharomyces cerevisiae is a good model organism for studies of xenobiotic metabolism.

Lang D, Kalgutkar AS (2003) Non-P450 mediated oxidative metabolism of xenobiotics. In Lee JS, Obach RS, Fisher MB (eds) Drug Metabolizing Enzymes. Marcel Dekker, New York, pp 483-539... 

Strolin-Benedetti, M., Whomsley, R., and Baltes, E. Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics. Expert Opin. Drug Metab. Toxicol. 2,895-921, 2006. 

Variability in the in vivo metabolism of a prototype drag that occurs when it is given to an individual on several occasions is an approach that we have used for assessing the influence of environment and life style on the metabolism of xenobiotics in humans (132,133). In these studies, we found that the amount of day-to-day variation in the oxidative metabolism of three prototype drags (phenylbutazone, antipyrine, and phenacetin) by seven healthy volunteers who... 

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