title: Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.
abstract: Through their unique oxidative chemistry, cytochrome P450 monooxygenases (CYPs) catalyze the elimination of most drugs and toxins from the human body. Protein-protein interactions play a critical role in this process. Historically, the study of CYP-protein interactions has focused on their electron transfer partners and allosteric mediators, cytochrome P450 reductase and cytochrome b5. However, CYPs can bind other proteins that also affect CYP function. Some examples include the progesterone receptor membrane component 1, damage resistance protein 1, human and bovine serum albumin, and intestinal fatty acid binding protein, in addition to other CYP isoforms. Furthermore, disruption of these interactions can lead to altered paths of metabolism and the production of toxic metabolites. In this review, we summarize the available evidence for CYP protein-protein interactions from the literature and offer a discussion of the potential impact of future studies aimed at characterizing noncanonical protein-protein interactions with CYP enzymes.
authors.affiliation: XenoTech, LLC , 16825 West 116th Street, Lenexa, Kansas 66219, United States.
authors.forename: Sylvie E
authors.initials: SE
authors.lastname: Kandel
authors.forename: Jed N
authors.initials: JN
authors.lastname: Lampe
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D015786:Cytochromes b5 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011980:Receptors, Progesterone / Q000737:chemistry / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D020033:Protein Isoforms; D011980:Receptors, Progesterone; D012709:Serum Albumin; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase