Open AccessExtensive protein interactions involving cytochrome P450 3A4: a possible contributor to the formation of a metabolosome
Author(s) -
Fujiwara Ryoichi,
Itoh Tomoo
Publication year - 2014
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.53
Subject(s) - cytochrome p450 , immunoprecipitation , microsome , biochemistry , gene isoform , chemistry , cyp3a4 , drug metabolism , enzyme , biology , gene
Cytochrome P450 ( CYP ) 3A4 is a membrane protein that catalyzes hydroxylation of endogenous and exogenous substrates. Protein–protein interaction is a crucial factor that regulates the function of enzymes. However, protein–protein interactions involving human CYP s have not been fully understood. In this study, extensive protein–protein interactions involving CYP 3A4 were determined by a shotgun analysis of immunoprecipitate utilizing anti‐ CYP 3A4 antibody. Our shotgun analysis revealed that 149 proteins were immunoprecipitated with anti‐ CYP 3A4 antibody in human liver microsomes. We further determined that 51 proteins of 149 proteins were specifically immunoprecipitated with the anti‐ CYP 3A4 antibody. Our analysis demonstrated that other CYP isoforms are interacting with CYP 3A4, which is in agreement with previous findings. Based on our current and previous findings, we propose that drug‐metabolizing enzymes such as CYP 3A4 and UDP ‐glucuronosyltransferase 2B7 form a metabolosome, which is a functional unit of metabolism consisting of multiple metabolism‐related proteins.