Cytochrome P450 Compound I: direct studies of the oxidant in P450s
Prof. Martin Newcomb
University of Illinois - Chicago
Tuesday, May 8, 2012 - 11:00am
Chemistry, Room 400 - (Prof. Garst B. Day)
Cytochrome P450 enzymes (P450s) are heme-containing enzymes that are ubiquitous in nature and the primary catalysts for oxidation reactions.
In humans, most drugs are metabolized by P450s in the liver. The transient oxidant formed in the P450s has not been detected in the natural reaction but has long been thought to be an oxoiron(IV) porphyrin radical cation termed Compound I by analogy to the known Compounds I in peroxidase enzymes.
P450 Compound I can be prepared by chemical oxidation and a photochemical oxidation method, and kinetic studies of Compounds I reactions are possible.
Kinetic studies of P450 Compounds I oxidations reveal a complex mechanistic picture with no H/D kinetic isotope effects and rate-limiting isomerization reactions under some conditions but not others. The current status of mechanistic studies of P450 Compounds I will be discussed.