Electrochemically Activated Catalytic Pathways of Human Metabolic Cytochrome P450s in Ultrathin Films

Among many enzymes containing the heme iron porphyrin cofactor, the cyt P450s represent a unique and important class of monooxygenases for their major role in drug and xenobiotic metabolism in humans. Cyt P450s are involved in human metabolism of about 75 % of all marketed drugs and there are about 57 isoforms of cyt P450s identified in humans [1, 2]. Some of the reactions catalyzed by cyt P450 enzymes include epoxidation, carbon hydroxylation, dealkylation, heteroatom oxygenation, and group transfer [3]. The attractive features of cyt P450s include their broad substrate specificity with unusual catalytic properties in catalyzing a wide variety of reactions with exquisite stereoselectivity [4]. Despite intense research efforts, the catalytic mechanisms of cyt P450s are not understood completely [1, 3, 5]. Nevertheless, significant progress has been made in understanding the redox chemistry of human cyt P450s and successfully obtaining crystal structures of various human cyt P450 isoforms [6–9]. Although differences in substrate specificities and redox properties and cellular locations of the membranous and