Evidence map›Paper›PMID 20071338›Full record

ArticleThe Journal of biological chemistry2010

Functional interactions between cytochromes P450 1A2 and 2B4 require both enzymes to reside in the same phospholipid vesicle: evidence for physical complex formation.

James R Reed, Marilyn Eyer, Wayne L Backes

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.5field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
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  8. Article
  9. Review
  10. Review
  11. Review
  12. Cytochrome P450 Organization and Function Are Modulated by Endoplasmic Reticulum Phospholipid Heterogeneity.Drug metabolism and disposition: the biological fate of chemicals · 2016
    Review
  13. Review
  14. Immobilized Cytochrome P450 for Monitoring of P450-P450 Interactions and Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2016
    Article
  15. The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function.Drug metabolism and disposition: the biological fate of chemicals · 2016
    Review
  16. Interaction Between Polymorphisms of IFN-γ and MICA Correlated with Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2016
    Article
  17. Article
  18. Article
  19. Article
  20. Review
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

3 authors at 1 institution in 1 country.

James R ReedDepartment of Pharmacology, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Marilyn Eyer
Wayne L Backes
Louisiana State University Health Sciences Center New Orleans · US

Funding

TOXICOLOGICAL SIGNIFICANCE OF ALKYLBENZENE METABOLISMR01ES004344 · NIEHS · LSU HEALTH SCIENCES CENTER · PI BACKES, WAYNE L · 1996 to 2013
$4.0M
NIEHS NIH HHS R01 ES004344NIEHS NIH HHS R01-ES004344
6 · The paper itself

Abstract

Previous studies have shown that the combined presence of two cytochrome P450 enzymes (P450s) can affect the function of both enzymes, results that are consistent with the formation of heteromeric P450.P450 complexes. The goal of this study was to provide direct evidence for a physical interaction between P450 1A2 (CYP1A2) and P450 2B4 (CYP2B4), by determining if the interactions required both enzymes to reside in the same lipid vesicles. When NADPH-cytochrome P450 reductase (CPR) and a single P450 were incorporated into separate vesicles, extremely slow reduction rates were observed, demonstrating that the enzymes were anchored in the vesicles. Next, several reconstituted systems were prepared: 1) CPR.CYP1A2, 2) CPR.CYP2B4, 3) a mixture of CPR.CYP1A2 vesicles with CPR.CYP2B4 vesicles, and 4) CPR.CYP1A2.CYP2B4 in the same vesicles (ternary system). When in the ternary system, CYP2B4-mediated metabolism was significantly inhibited, and CYP1A2 activities were stimulated by the presence of the alternate P450. In contrast, P450s in separate vesicles were unable to interact. These data demonstrate that P450s must be in the same vesicles to alter metabolism. Additional evidence for a physical interaction among CPR, CYP1A2, and CYP2B4 was provided by cross-linking with bis(sulfosuccinimidyl) suberate. The results showed that after cross-linking, antibody to CYP1A2 was able to co-immunoprecipitate CYP2B4 but only when both proteins were in the same phospholipid vesicles. These results clearly demonstrate that the alterations in P450 function require both P450s to be present in the same vesicles and support a mechanism whereby P450s form a physical complex in the membrane.

Indexed as

AnimalsAryl Hydrocarbon HydroxylasesBiological TransportCattleChromatography, GelCross-Linking ReagentsCytochrome P-450 CYP1A2Cytochrome P450 Family 2ImmunoprecipitationMicrosomes, LiverPhosphatidylcholinesPhospholipidsProtein IsoformsRabbitsSubstrate SpecificityTime FactorsAryl Hydrocarbon HydroxylasesCross-Linking ReagentsCytochrome P-450 CYP1A2cytochrome P-450 CYP2B4 (rabbit)Cytochrome P450 Family 2PhosphatidylcholinesPhospholipidsProtein Isoforms

Identifiers

PMID20071338
PMCPMC2838316
OpenAlexW2021193295

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.