Abstract:
: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.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Ishii Y,Iwanaga M,Nishimura Y,Takeda S,Ikushiro S,Nagata K,Yamazoe Y,Mackenzie PI,Yamada Hdoi
10.2133/dmpk.22.367subject
Has Abstractpub_date
2007-10-01 00:00:00pages
367-76issue
5eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/22.367journal_volume
22pub_type
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