Inquiry of Literature Evidence for Induced Fit of Cytochrome P450 2C9 for Warfarin, Phenprocoumon, Flurbiprofen and Clopidogrel: A Critical Review
Cytochrome P450 oxygenases (CYP for short) are liver microsomal enzymes with a prosthetic hem(e) group that catalyze various types of hepatic biotransformation reactions including aromatic and aliphatic oxidation, N- and O-dealkylation, S- and N-oxidation, sulfoxide/sulfone formation, oxidative deamination, desulfuration, and dehalogenation [1,2]. Almost 90% of commonly used drugs are metabolized by CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 . They metabolize a remarkably diverse group of endogenous substrates as well as (exogenous) xenobiotics, like nutrients, plant ingredients, microbial toxins, or synthetic drugs. They are sometimes referred to as isoenzymes – a fairly inappropriate terminology because they do not always share the same catalytic reaction, i.e. neither mechanisms nor substrates. Nevertheless, its name P450 was properly attributed to these heme proteins alluding to the Protein’s visible 450 nm spectral absorption line observed after chemical reduction and exposure to carbon monoxide gas for analytical characterization . Here we restricted the bibliographic search on cases related to drug biotransformation by hydroxylation of warfarin, phenprocoumon, flurbiprofen, ritonavir and clopidogrel.