Cytochrome p450 enzymes and electrochemistry: crosstalk with electrodes as redox partners and electron sources.

Abstract

The functional significance of cytochrome P450 (P450) enzymes includes their ability to catalyze the biotransformation of xenobiotics (foreign compounds) and endogenous compounds. P450 enzymes play an important role in the detoxification of exogenous bioactive compounds and hydrophobic xenobiotics (e.g. carcinogens, drugs, environment pollutants, food supplements, medicines, plant products) and in the biotransformation of endogenous bioactive compounds (e.g. amino acids, cholesterol, eicosanoids, saturated/unsaturated fatty acids, melatonin, steroid hormones). Electrode/P450 systems are analyzed in terms of the mechanisms underlying P450-catalyzed reactions. Bioelectrocatalysis-based screening of potential substrates or inhibitors of P450 enzymes, the stoichiometry of the electrocatalytic cycle, oxidation-reduction (redox) thermodynamics, and the peroxide shunt pathway are described. Electrochemical techniques are utilized for investigating the influence of (1) the vitamin B group, (2) vitamins (e.g. vitamins A and B) and antioxidants (e.g. taurine), and (3) drugs and antioxidants (e.g. mexidol, ethoxidol) on biocatalysis using P450 enzymes, and on the metabolism of drugs catalyzed by P450 3A4. The characteristics, performance and potential applications of P450 electrochemical systems are also discussed.