Evidence map›Paper›PMID 24893149›Full record

ArticleBiochemistry2014

ATP allosterically activates the human 5-lipoxygenase molecular mechanism of arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid.

Christopher J Smyrniotis, Shannon R Barbour, Zexin Xia, Mark S Hixon, Theodore R Holman

Abstract read
In one paragraph

Article in Biochemistry, 2014. 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
0.8field-weighted citation impact, top 26% 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, 39 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Lipoxygenases at the Intersection of Infection and Carcinogenesis.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020
    Review
  16. Review
  17. Review
  18. Article
  19. Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018
    Review
  20. Article
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

5 authors at 2 institutions in 1 country.

Christopher J SmyrniotisDepartment of Chemistry and Biochemistry, University of California , Santa Cruz, California 95064, United States.
Shannon R Barbour
Zexin Xia
Mark S Hixon
Theodore R Holman
University of California, Santa Cruz · USTakeda (United States) · US

Funding

Functional and Inhibitory Studies of Human LipoxygenaseR01GM056062 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HOLMAN, THEODORE R · 2002 to 2012
$3.1M
THERMO ELECTRON LTQ-FT MASS SPECTROMETERS10RR020939 · NCRR · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HOLMAN, THEODORE R · 2006 to 2006
$368k
FUNCTIONAL STUDIES OF HUMAN AND SOYBEAN LIPOXYGENASER29GM056062 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HOLMAN, THEODORE R · 1997 to 2001
$206k
NCRR NIH HHS S10 RR020939NCRR NIH HHS S10-RR20939NIGMS NIH HHS GM56062NIGMS NIH HHS R01 GM056062
6 · The paper itself

Abstract

5-Lipoxygenase (5-LOX) reacts with arachidonic acid (AA) to first generate 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid [5(S)-HpETE] and then an epoxide from 5(S)-HpETE to form leukotriene A4, from a single polyunsaturated fatty acid. This work investigates the kinetic mechanism of these two processes and the role of ATP in their activation. Specifically, it was determined that epoxidation of 5(S)-HpETE (dehydration of the hydroperoxide) has a rate of substrate capture (Vmax/Km) significantly lower than that of AA hydroperoxidation (oxidation of AA to form the hydroperoxide); however, hyperbolic kinetic parameters for ATP activation indicate a similar activation for AA and 5(S)-HpETE. Solvent isotope effect results for both hydroperoxidation and epoxidation indicate that a specific step in its molecular mechanism is changed, possibly because of a lowering of the dependence of the rate-limiting step on hydrogen atom abstraction and an increase in the dependency on hydrogen bond rearrangement. Therefore, changes in ATP concentration in the cell could affect the production of 5-LOX products, such as leukotrienes and lipoxins, and thus have wide implications for the regulation of cellular inflammation.

Indexed as

Adenosine TriphosphateAllosteric RegulationArachidonate 5-LipoxygenaseArachidonic AcidCalciumEnzyme ActivationEpoxy CompoundsHumansLeukotriene A4LeukotrienesPeroxidesStereoisomerismViscosityAdenosine TriphosphateArachidonate 5-LipoxygenaseArachidonic Acidarachidonic acid 5-hydroperoxideCalciumEpoxy CompoundsLeukotriene A4LeukotrienesPeroxides

Identifiers

PMID24893149
PMCPMC4215895
OpenAlexW2315873193

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.