Evidence map›Paper›PMID 31750875›Full record

ArticleThe Biochemical journal2019

Toward a systems approach to cytochrome P450 ensemble: interactions of CYP2E1 with other P450 species and their impact on CYP1A2.

Nadezhda Y Davydova, Bikash Dangi, Marc A Maldonado, Nikita E Vavilov, Victor G Zgoda, Dmitri R Davydov

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In one paragraph

Article in The Biochemical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
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

20 citing papers in PubMed, 30 citations in OpenAlex.

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  16. Multienzyme Kinetics and Sequential Metabolism.Methods in molecular biology (Clifton, N.J.) · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Nadezhda Y DavydovaDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
Bikash DangiDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
Marc A MaldonadoDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
Nikita E VavilovInstitute of Biomedical Chemistry, Moscow 119121, Russia.
Victor G ZgodaInstitute of Biomedical Chemistry, Moscow 119121, Russia.
Dmitri R DavydovDepartment of Chemistry, Washington State University, Pullman, WA 99164, U.S.A.
Washington State University · USInstitute of Biomedical Chemistry · RU

Funding

Non-canonical Role of Ethanol-Inducible Cytochrome P450 Species in Alcohol-Drug Interactions and Alcohol-Related DisordersR21AA024548 · NIAAA · WASHINGTON STATE UNIVERSITY · PI DAVYDOV, DMITRI R, JONES, JEFFREY P · 2018 to 2019
$402k
NIAAA NIH HHS R21 AA024548
6 · The paper itself

Abstract

In this study, we investigate the ability of ethanol-inducible CYP2E1 to interact with other cytochrome P450 species and affect the metabolism of their substrates. As a model system, we used CYP2E1-enriched human liver microsomes (HLM) obtained by the incorporation of purified CYP2E1. Using a technique based on homo-FRET in oligomers of CYP2E1 labeled with BODIPY 577/618 maleimide we demonstrated that the interactions of CYP2E1 with HLM result in the formation of its mixed oligomers with other P450 species present in the microsomal membrane. Incorporation of CYP2E1 results in a multifold increase in the rate of metabolism of CYP2E1-specific substrates p-Nitrophenol and Chlorzaxozone. The rate of their oxidation remains proportional to the amount of incorporated CYP2E1 up to the content of 0.3-0.4 nmol/mg protein (or ∼50% CYP2E1 in the P450 pool). The incorporated CYP2E1 becomes a fully functional member of the P450 ensemble and do not exhibit any detectable functional differences with the endogenous CYP2E1. Enrichment of HLM with CYP2E1 results in pronounced changes in the metabolism of 7-ethoxy-4-cyanocoumarin (CEC), the substrate of CYP2C19 and CYP1A2 suggesting an increase in the involvement of the latter in its metabolism. This effect goes together with an augmentation of the rate of dealkylation of CYP1A2-specific substrate 7-ethoxyresorufin. Furthermore, probing the interactions of CYP2E1 with model microsomes containing individual P450 enzymes we found that CYP2E1 efficiently interacts with CYP1A2, but lacks any ability to form complexes with CYP2C19. This finding goes inline with CYP2E1-induced redirection of the main route of CEC metabolism from CYP2C19 to CYP1A2.

Indexed as

Cell MembraneCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C19Cytochrome P-450 CYP2E1DealkylationEscherichia coliFemaleHumansLiverMaleMass SpectrometryMicrosomes, LiverNADPH-Ferrihemoprotein ReductaseOxazinesOxidation-ReductionSpectrometry, FluorescenceCYP1A2 protein, humanCYP2C19 protein, humanCytochrome P-450 CYP1A2Cytochrome P-450 CYP2C19Cytochrome P-450 CYP2E1ethoxyresorufinNADPH-Ferrihemoprotein ReductaseOxazinesalcohol–drug interactionscytochrome p450drug metabolismoligomerizationprotein–protein interactions

Identifiers

PMID31750875
PMCPMC7085345
OpenAlexW2991133457

What OpenQuestion holds

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Read underepoch 390

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.