Protein-protein interactions between rat hepatic cytochromes P450 (P450s) and UDP-glucuronosyltransferases (UGTs): evidence for the functionally active UGT in P450-UGT complex

Drug Metab Pharmacokinet. 2007 Oct;22(5):367-76. doi: 10.2133/dmpk.22.367.


The interaction between cytochrome P450s (CYP, P450) and UDP-glucuronosyltransferases (UGTs) was studied by co-immunoprecipitation. P450 isoform-selective antibody was used as a probe to co-precipitate UGTs with the P450s from solubilized rat liver microsomes. Antibodies toward CYP3A2, CYP2B2, CYP2C11/13 and CYP1A2 co-precipitated UGTs with corresponding P450s. However, calnexin, a type-I membrane protein, in the endoplasmic reticulum was not co-precipitated by anti-P450 antibodies. UGT activity toward 4-methylumbelliferone was detected in all co-precipitates, suggesting that UGT in the complex with P450s is functionally active. Repeated washing of co-immunoprecipitates revealed differences among P450 isoforms with regard to the affinity for UGT. Larger amounts of UGT1A1 and UGT1A6, compared with UGT2B1, were washed out from UGTs-CYP2C11/13 co-precipitates, whereas UGT-CYP3A2 and UGT-CYP2Bs complexes were resistant to thorough washing. Thus, CYP2C11/13 could associate with UGTs, but the affinity is assumed to be weaker than that of CYP2B/3As. These results suggest that there is isoform specificity in the interaction between P450s and UGTs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome P450 Family 2
  • Cytochromes
  • Glucuronosyltransferase / metabolism*
  • Hymecromone / analogs & derivatives
  • Hymecromone / metabolism
  • Immunoprecipitation
  • Male
  • Membrane Proteins / metabolism
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism*
  • Multienzyme Complexes / metabolism
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Steroid 16-alpha-Hydroxylase / metabolism
  • Steroid Hydroxylases / metabolism
  • Substrate Specificity


  • Cytochromes
  • Membrane Proteins
  • Multienzyme Complexes
  • Ugt1a1 protein, rat
  • Hymecromone
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C11 protein, rat
  • Cyp1a2 protein, rat
  • Cyp2c13 protein, rat
  • Cyp3a2 protein, rat
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • Cytochrome P450 Family 2
  • Steroid 16-alpha-Hydroxylase
  • steroid 16-beta-hydroxylase
  • Glucuronosyltransferase
  • UDP-glucuronosyltransferase, UGT1A7