UDP-Glucuronosyltransferase (UGT)-mediated attenuations of cytochrome P450 3A4 activity: UGT isoform-dependent mechanism of suppression.

ABSTRACT:

Background and purpose

Cytochrome P450 (CYP, P450) 3A4 is involved in the metabolism of 50% of drugs and its catalytic activity in vivo is not explained only by hepatic expression levels. We previously demonstrated that UDP-glucuronosyltransferase (UGT) 2B7 suppressed CYP3A4 activity through an interaction. In the present study, we target UGT1A9 as another candidate modulator of CYP3A4.

Experimental approach

We prepared co-expressed enzymes using the baculovirus-insect cell expression system and compared CYP3A4 activity in the presence and absence of UGT1A9. Wistar rats were treated with dexamethasone and liver microsomes were used to elucidate the role of CYP3A-UGT1A interactions.

Key results

UGT1A9 and UGT2B7 interacted with and suppressed CYP3A4. Kinetic analyses s

SUBMITTER: Miyauchi Y 

PROVIDER: S-EPMC7042106 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature