Interaction between cytochrome P450 and other drug-metabolizing enzymes: Evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase

Ken ichiro Taura, Hideyuki Yamada, Yukiko Hagino, Yuji Ishii, Masa aki Mori, Kazuta Oguri

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium cholate-solubilized microsomes from phenobarbital-treated rat liver were applied to the columns and the material eluted with buffer containing NaCl was analyzed by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP-glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no ability to retain these proteins. Protein disulfide isomerase and calnexin, non-drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to associate with the CYP1A1 column. These results suggest that CYP1A1 interacts with mEH and UGT to facilitate a series of multistep drug metabolic conversions. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)1048-1052
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume273
Issue number3
DOIs
Publication statusPublished - Jul 14 2000

Fingerprint

Epoxide Hydrolases
Glucuronosyltransferase
Cytochrome P-450 CYP1A1
Cytochrome P-450 Enzyme System
Association reactions
Enzymes
Bovine Serum Albumin
Pharmaceutical Preparations
Glycine
Calnexin
Sodium Cholate
Protein Disulfide-Isomerases
Affinity chromatography
NADPH-Ferrihemoprotein Reductase
Proteins
Phenobarbital
Microsomes
Affinity Chromatography
Immunoblotting
Endoplasmic Reticulum

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Interaction between cytochrome P450 and other drug-metabolizing enzymes : Evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase. / Taura, Ken ichiro; Yamada, Hideyuki; Hagino, Yukiko; Ishii, Yuji; Mori, Masa aki; Oguri, Kazuta.

In: Biochemical and Biophysical Research Communications, Vol. 273, No. 3, 14.07.2000, p. 1048-1052.

Research output: Contribution to journalArticle

@article{db2bf922439c4f05822a2d2c0fa48183,
title = "Interaction between cytochrome P450 and other drug-metabolizing enzymes: Evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase",
abstract = "Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium cholate-solubilized microsomes from phenobarbital-treated rat liver were applied to the columns and the material eluted with buffer containing NaCl was analyzed by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP-glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no ability to retain these proteins. Protein disulfide isomerase and calnexin, non-drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to associate with the CYP1A1 column. These results suggest that CYP1A1 interacts with mEH and UGT to facilitate a series of multistep drug metabolic conversions. (C) 2000 Academic Press.",
author = "Taura, {Ken ichiro} and Hideyuki Yamada and Yukiko Hagino and Yuji Ishii and Mori, {Masa aki} and Kazuta Oguri",
year = "2000",
month = "7",
day = "14",
doi = "10.1006/bbrc.2000.3076",
language = "English",
volume = "273",
pages = "1048--1052",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Interaction between cytochrome P450 and other drug-metabolizing enzymes

T2 - Evidence for an association of CYP1A1 with microsomal epoxide hydrolase and UDP-glucuronosyltransferase

AU - Taura, Ken ichiro

AU - Yamada, Hideyuki

AU - Hagino, Yukiko

AU - Ishii, Yuji

AU - Mori, Masa aki

AU - Oguri, Kazuta

PY - 2000/7/14

Y1 - 2000/7/14

N2 - Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium cholate-solubilized microsomes from phenobarbital-treated rat liver were applied to the columns and the material eluted with buffer containing NaCl was analyzed by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP-glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no ability to retain these proteins. Protein disulfide isomerase and calnexin, non-drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to associate with the CYP1A1 column. These results suggest that CYP1A1 interacts with mEH and UGT to facilitate a series of multistep drug metabolic conversions. (C) 2000 Academic Press.

AB - Protein-protein interactions between cytochrome P450 (P450) and other drug-metabolizing enzymes were studied by affinity chromatography using CYP1A1-, glycine-, and bovine serum albumin (BSA)-conjugated Sepharose 4B columns. Sodium cholate-solubilized microsomes from phenobarbital-treated rat liver were applied to the columns and the material eluted with buffer containing NaCl was analyzed by immunoblotting. Microsomal epoxide hydrolase (mEH) and UDP-glucuronosyltransferases (UGTs), as well as NADPH-P450 reductase, were efficiently trapped by the CYP1A1 column. Glycine and BSA columns exhibited no ability to retain these proteins. Protein disulfide isomerase and calnexin, non-drug-metabolizing enzymes expressed in the endoplasmic reticulum, were unable to associate with the CYP1A1 column. These results suggest that CYP1A1 interacts with mEH and UGT to facilitate a series of multistep drug metabolic conversions. (C) 2000 Academic Press.

UR - http://www.scopus.com/inward/record.url?scp=0034647835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034647835&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2000.3076

DO - 10.1006/bbrc.2000.3076

M3 - Article

C2 - 10891369

AN - SCOPUS:0034647835

VL - 273

SP - 1048

EP - 1052

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -