Evidence map›Paper›PMID 21659470›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2011

Polymorphic variants of cytochrome P450 2B6 (CYP2B6.4-CYP2B6.9) exhibit altered rates of metabolism for bupropion and efavirenz: a charge-reversal mutation in the K139E variant (CYP2B6.8) impairs formation of a functional cytochrome p450-reductase complex.

Haoming Zhang, Chitra Sridar, Cesar Kenaan, Hemali Amunugama, David P Ballou, Paul F Hollenberg

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

Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
10.5field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 63 citations in OpenAlex.

  1. Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion.Drug metabolism and disposition: the biological fate of chemicals · 2024
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  16. Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry.Drug metabolism and disposition: the biological fate of chemicals · 2019
    Review
  17. Article
  18. Article
  19. The Prevalence ofOsong public health and research perspectives · 2018
    Article
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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 1 institution in 1 country.

Haoming ZhangDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-5632, USA.
Chitra Sridar
Cesar Kenaan
Hemali Amunugama
David P Ballou
Paul F Hollenberg
University of Michigan–Ann Arbor · US

Funding

NCI NIH HHS CA16945
6 · The paper itself

Abstract

In this study, metabolism of bupropion, efavirenz, and 7-ethoxy-4-trifluoromethylcoumarin (7-EFC) by CYP2B6 wild type (CYP2B6.1) and six polymorphic variants (CYP2B6.4 to CYP2B6.9) was investigated in a reconstituted system to gain a better understanding of the effects of the mutations on the catalytic properties of these naturally occurring variants. All six variants were successfully overexpressed in Escherichia coli, including CYP2B6.8 (the K139E variant), which previously could not be overexpressed in mammalian COS-1 cells (J Pharmacol Exp Ther 311:34-43, 2004). The steady-state turnover rates for the hydroxylation of bupropion and efavirenz and the O-deethylation of 7-EFC showed that these mutations significantly alter the catalytic activities of CYP2B6. It was found that CYP2B6.6 exhibits 4- and 27-fold increases in the K(m) values for the hydroxylation of bupropion and efavirenz, respectively, and CYP2B6.8 completely loses its ability to metabolize any of the substrates under normal turnover conditions. However, compared with CYP2B6.1, CYP2B6.8 retains 77% of its 7-EFC O-deethylase activity in the presence of tert-butyl hydroperoxide as an alternative oxidant, indicating that the heme and the active site are catalytically competent. Presteady-state measurements of the rate of electron transfer from NADPH-dependent cytochrome P450 reductase (CPR) to CYP2B6.8 using stopped-flow spectrophotometry revealed that CYP2B6.8 is incapable of accepting electrons from CPR. These observations provide conclusive evidence suggesting that the charge-reversal mutation in the K139E variant prevents CYP2B6.8 from forming a functional complex with CPR. Results from this work provide further insights to better understand the genotype-phenotype correlation regarding CYP2B6 polymorphisms and drug metabolism.

Indexed as

AlkynesAnimalsAntidepressive Agents, Second-GenerationAnti-HIV AgentsAryl Hydrocarbon HydroxylasesBenzoxazinesBupropionCatalysisChlorocebus aethiopsCOS CellsCoumarinsCyclopropanesCytochrome P-450 CYP2B6Electron TransportEscherichia coliFerric Compounds7-ethoxy-4-trifluoromethylcoumarinAlkynesAntidepressive Agents, Second-GenerationAnti-HIV AgentsAryl Hydrocarbon HydroxylasesBenzoxazinesBupropionCoumarinsCyclopropanesCytochrome P-450 CYP2B6efavirenzFerric CompoundsNADPH-Ferrihemoprotein ReductaseOxidoreductases, N-Demethylatingtert-Butylhydroperoxide

Identifiers

PMID21659470
PMCPMC3164347
OpenAlexW2115440722

What OpenQuestion holds

Textmetadata
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.