Evidence map›Paper›PMID 24591617›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota.

Yijun Zhu, Eleanor Jameson, Marialuisa Crosatti, Hendrik Schäfer, Kumar Rajakumar, Timothy D H Bugg, Yin Chen

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
213citing papers in PubMed, 3 pooled it
10.4field-weighted citation impact, top 1% 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

213 citing papers in PubMed, 3 syntheses or guidelines pooled it, 368 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trimethylamine-Nutrients · 2020
    Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

153 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Yijun ZhuSchool of Life Sciences and Department of Chemistry, University of Warwick, Coventry CV4 7AL, United Kingdom.
Eleanor Jameson
Marialuisa Crosatti
Hendrik Schäfer
Kumar Rajakumar
Timothy D H Bugg
Yin Chen
University of Leicester · GBUniversity of Warwick · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dietary intake of L-carnitine can promote cardiovascular diseases in humans through microbial production of trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although our microbiota are responsible for TMA formation from carnitine, the underpinning molecular and biochemical mechanisms remain unclear. In this study, using bioinformatics approaches, we first identified a two-component Rieske-type oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved in carnitine metabolism in representative genomes of the human microbiota. CntA belongs to a group of previously uncharacterized Rieske-type proteins and has an unusual "bridging" glutamate but not the aspartate residue, which is believed to facilitate intersubunit electron transfer between the Rieske center and the catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we then demonstrate that cntAB is essential in carnitine degradation to TMA. Heterologous overexpression of cntAB enables Escherichia coli to produce TMA, confirming that these genes are sufficient in TMA formation. Site-directed mutagenesis experiments have confirmed that this unusual "bridging glutamate" residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is able to produce TMA. Taken together, the data in our study reveal the molecular and biochemical mechanisms underpinning carnitine metabolism to TMA in human microbiota and assign the role of this novel group of Rieske-type proteins in microbial carnitine metabolism.

Indexed as

Acinetobacter baumanniiCarnitineChromatography, Ion ExchangeComputational BiologyEscherichia coliHumansMethylaminesMicrobiotaMutagenesis, Site-DirectedOxidoreductasesOxygenasesSpectrophotometry, UltravioletCarnitineMethylaminesOxidoreductasesOxygenasestrimethylaminecomparative genomicsgut microbiotamethylated amine metabolism

Identifiers

PMID24591617
PMCPMC3964110
OpenAlexW2000670099

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.