Evidence map›Paper›PMID 41727125›Full record

ArticlebioRxiv : the preprint server for biology2026

The role of CYP3A-CYP2E1 interactions in activation of CYP3A enzymes by chronic alcohol exposure.

Dmitri R Davydov, Kannapiran Ponraj, Nadezhda Davydova, Guihua Yue, Dilip Kumar Singh, Arpita Guha Neogi, Kari A Gaither, Bhagwat Prasad

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Dmitri R DavydovDepartment of Chemistry, Washington State University, Pullman, WA, 99164.ORCID 0000-0001-8520-0033
Kannapiran PonrajDepartment of Chemistry, Washington State University, Pullman, WA, 99164.
Nadezhda DavydovaDepartment of Chemistry, Washington State University, Pullman, WA, 99164.
Guihua YueDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202.
Dilip Kumar SinghDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229.
Arpita Guha NeogiDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202.
Kari A GaitherDepartment of Chemistry, Washington State University, Pullman, WA, 99164.ORCID 0000-0003-2014-4362
Bhagwat PrasadDivision of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229.ORCID 0000-0002-9090-0912

Funding

Inter-Enzyme Crosstalk in the Cytochrome P450 Ensemble: Implications for the Effects of Alcohol on Drug Metabolism and Alcohol-Drug InteractionsR01AA030155 · NIAAA · WASHINGTON STATE UNIVERSITY · PI DAVYDOV, DMITRI R, PRASAD, BHAGWAT · 2022 to 2025
$2.0M
NIAAA NIH HHS R01 AA030155
6 · The paper itself

Abstract

Aiming to examine the effect of chronic alcohol exposure on the activity of CYP3A enzymes in human liver, we studied the metabolism of two CYP3A-specific substrates, 7-benzyloxyquinoline (7-BQ) and ivermectin, in 23 preparations of human liver microsomes (HLM) obtained from donors with documented alcohol exposure, graded from non-drinkers to heavy alcoholics. All HLM samples were characterized for the composition of the cytochrome P450 pool and the abundances of other drug-metabolizing and endoplasmic reticulum-stress-related enzymes by global proteomics. Our studies revealed a striking increase in the activities of CYP3A enzymes caused by chronic alcohol exposure. This effect is not associated with CYP3A enzyme levels, which do not correlate with alcohol exposure. Instead, the rates of 7-BQ and ivermectin metabolism correlate with the content of alcohol-inducible CYP2E1. However, this enzyme does not metabolize ivermectin, and its activity with 7-BQ is negligible. These results suggest that the observed acceleration of the elimination of drugs metabolized by CYP3A enzymes by alcohol exposure is due to functional effects of the interaction between CYP3A and CYP2E1. To elucidate the potential mechanism of this effect, we studied the formation of CYP2E1-CYP3A4 complexes in CYP3A4-containing Supersomes with co-incorporated CYP2E1 using tag-transfer chemical crosslinking mass spectrometry (CX-MS). These experiments confirmed physical interactions between the proteins and allowed the identification of CYP3A4 residues at the sites of contact. This information was used to build structural models of the CYP2E1-CYP3A4 complex and to propose possible mechanisms for the observed effects.

Indexed as

7-benzyloxyquinolinealcoholalcohol consumptionalcohol-drug interactionscrosslinking mass spectrometryCYP2E1CYP3A4CYP3A5cytochrome P450drug metabolismhuman liver microsomesivermectinNADPH-cytochrome P450 reductaseprotein cross-linkingprotein-protein interactions

Identifiers

PMID41727125
PMCPMC12919093

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.