Regulation Mechanisms of Xenobiotics Metabolizing Liver Cytochrome P-450 and Toxicological Implications

Cytochromes P-450 exhibit a key function in the biotransformation of xenobiotics [13]. Depending on the chemical nature of the foreign compounds, either a detoxification or a toxic activation is effected by the enzymes. The enzyme action is connected with the reductive splitting of molecular oxygen and the insertion of an oxygen atom into the substrate, thus converting a hydrophobic compound into a more polar product. The excretion of such a transformed compound is facilitated. The insertion of a reactive group into the molecule, however, induces the possibility of its covalent binding to proteins and nucleic acids resulting in toxic effects, even in mutagenesis and carcinogenesis. Besides this oxidative metabolism, cytochrome P-450 also catalyzes the reductive transformation of foreign compounds. This type of pathway mostly results in toxification since reactive free radicals are formed.