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

Yuji Ishii, Megumi Iwanaga, Yoshio Nishimura, Shuso Takeda, Shin Ichi Ikushiro, Kiyoshi Nagata, Yasushi Yamazoe, Peter I. Mackenzie, Hideyuki Yamada

研究成果: ジャーナルへの寄稿学術誌査読

34 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)367-376
ページ数10
ジャーナルDrug metabolism and pharmacokinetics
22
5
DOI
出版ステータス出版済み - 10月 2007

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学
  • 薬理学(医学)

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