Evidence map›Paper›PMID 33197431›Full record

ArticleArchives of biochemistry and biophysics2021

Effects of alcohol-induced increase in CYP2E1 content in human liver microsomes on the activity and cooperativity of CYP3A4.

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

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of biochemistry and biophysics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Bikash DangiDepartment of Chemistry, Washington State University, Pullman, WA, 99164, USA.
Nadezhda Y DavydovaDepartment of Chemistry, Washington State University, Pullman, WA, 99164, USA.
Marc A MaldonadoDepartment of Chemistry, Washington State University, Pullman, WA, 99164, USA.
Armina AbbasiDepartment of Chemistry, Washington State University, Pullman, WA, 99164, USA.
Nikita E VavilovInstitute of Biomedical Chemistry, Moscow, 119121, Russia.
Victor G ZgodaInstitute of Biomedical Chemistry, Moscow, 119121, Russia; Skolkovo Institute of Science and Technology, 143025, Skolkovo, Moscow Region, Russia.
Dmitri R DavydovDepartment of Chemistry, Washington State University, Pullman, WA, 99164, USA. Electronic address: dmrdavyd@gmail.com.
Washington State University · USInstitute of Biomedical Chemistry · RUSkolkovo Institute of Science and Technology · 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

We investigate the effect of the alcohol-induced increase in the content of CYP2E1 in human liver microsomes (HLM) on the function of CYP3A4. Membrane incorporation of the purified CYP2E1 into HLM considerably increases the rate of metabolism of 7-benzyloxyquinoline (BQ) and attenuates the homotropic cooperativity observed with this CYP3A4-specific substrate. It also eliminates the activating effect of α-naphthoflavone (ANF) seen in some HLM samples. To probe the physiological relevance of these effects, we compared three pooled preparations of HLM from normal donors (HLM-N) with a pooled preparation from ten heavy alcohol consumers (HLM-A). The composition of the P450 pool in all samples was characterized by the mass-spectrometric determination of 11 cytochrome P450 species. The fractional content of CYP2E1 in HLM-A was from 2.0 to 3.4 times higher than in HLM-N. In contrast, the content of CYP3A4 in HLM-A was the lowest among all samples. Despite that, HLM-A exhibited a much higher metabolism rate and a lower homotropic cooperativity with BQ, similar to CYP2E1-enriched HLM-N. To substantiate the involvement of interactions between CYP2E1 and CYP3A4 in these effects, we probed hetero-association of these proteins in CYP3A4-containing Supersomes™ with a technique employing CYP2E1 labeled with BODIPY-618 maleimide. These experiments evinced the interactions between the two enzymes and revealed an inhibitory effect of ANF on their association. Our results demonstrate that the functional properties of CYP3A4 are fundamentally dependent on the composition of the cytochrome P450 ensemble and suggest a possible impact of chronic alcohol exposure on the pharmacokinetics of drugs metabolized by CYP3A4.

Indexed as

Amino Acid SequenceAmitriptylineBenzoflavonesCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AEnzyme ActivatorsEthanolFemaleHumansIvermectinMaleMicrosomes, LiverMidazolamNitrophenolsQuinolines4-nitrophenol7-benzyloxyquinolinealpha-naphthoflavoneAmitriptylineBenzoflavonesCYP3A4 protein, humanCytochrome P-450 CYP2E1Cytochrome P-450 CYP3AEnzyme ActivatorsEthanolIvermectinMidazolamNitrophenolsQuinolinesAlcohol-drug interactionsAlcohol exposureCooperativityCYP2E1CYP3A4Cytochrome P450OligomerizationProtein-protein interaction

Identifiers

PMID33197431
PMCPMC7856178
OpenAlexW3101858956

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.