ИСТИНА

Electrochemically driven cytochrome P450 (CYP) systems execute the dual function: substitute partner proteins and serve as a source of electrons for catalysis. Electrochemical CYP systems were applied to studying the catalytic activity, drug metabolism profiling, searching of substrate/inhibitor potential of newly synthesized chemicals, modulating of coupling efficiency, drug-drug interactions, the stoichiometry and the thermodynamics of the catalytic cycle. In electrochemical experiments, “in electrode” model system the catalytic current is an adequate expression of the enzymatic reaction. Electrocatalytic activity of mammalian cytochromes P450 2B4, 1A2, 3A4, 51b1 (sterol14α-demethylase Mycobacterium tuberculosis CYP51b1), 11A1 (P450scc), 2C9, 2D6, 17A1 were studied using different types of modified electrodes. The drug-drug interactions for mammalian CYP3A4, CYP2C9 and CYP2D6 were studied for diclofenac, erythromycin, testosterone, metabolic antioxidant preparations such as ethoxidol (2-ethyl-6-methyl-3-hydroxypyridine malate), mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate), cytochrome c, L-carnitine, , taurine, antihypoxant mildronate. Drug electroxidation was used for estimation of drug determination. These findings provide data for future clinical risk prediction studies – especially for those devoted to the interaction of drugs with antioxidants and antihypoxants. Electrochemically driven CYP reactions may have practically relevant providing a useful tool for drug assay studies. (p. 80)