Evidence map›Paper›PMID 20686576›Full record

ArticleNature2010

Branched tricarboxylic acid metabolism in Plasmodium falciparum.

Kellen L Olszewski, Michael W Mather, Joanne M Morrisey, Benjamin A Garcia, Akhil B Vaidya, Joshua D Rabinowitz, Manuel Llinás

RetractedErratum issuedOpen access · greenAbstract readRetracted Publication
In one paragraph

Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
25.8field-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

59 citing papers in PubMed, 120 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Kellen L OlszewskiDepartment of Molecular Biology and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Michael W Mather
Joanne M Morrisey
Benjamin A Garcia
Akhil B Vaidya
Joshua D Rabinowitz
Manuel Llinás
Princeton University · USDrexel University · US

Funding

Spatial Patterning During DevelopmentP50GM071508 · NIGMS · PRINCETON UNIVERSITY · PI POWELL, SUSAN M · 2004 to 2013
$30.6M
ORGANELLE GENOMES OF MALARIAL PARASITESR01AI028398 · NIAID · MCP HAHNEMANN UNIVERSITY · PI AKHIL B VAIDYA · 1989 to 2026
$10.1M
Novel antimalarial strategies using metabolomic network discoveryDP2OD001315 · OD · PRINCETON UNIVERSITY · PI LLINAS, MANUEL · 2007 to 2007
$2.4M
Metabolomics of the Virus-host Cell InteractionR01AI078063 · NIAID · PRINCETON UNIVERSITY · PI RABINOWITZ, JOSHUA D · 2007 to 2010
$1.2M
Mitochondrial Functions in Malaria ParasitesR56AI028398 · NIAID · DREXEL UNIVERSITY · PI VAIDYA, AKHIL B · 2016 to 2016
$512k
ORGANELLE GENOMES OF MALARIAL PARASITESR22AI028398 · NIAID · HAHNEMANN UNIVERSITY · PI VAIDYA, AKHIL B · 1989 to 1991
–
NIAID NIH HHS AI028398NIAID NIH HHS R01 AI028398NIAID NIH HHS R01 AI078063NIAID NIH HHS R56 AI028398NIGMS NIH HHS P50 GM071508NIH HHS 1DP2OD001315-01NIH HHS DP2 OD001315
6 · The paper itself

Abstract

A central hub of carbon metabolism is the tricarboxylic acid cycle, which serves to connect the processes of glycolysis, gluconeogenesis, respiration, amino acid synthesis and other biosynthetic pathways. The protozoan intracellular malaria parasites (Plasmodium spp.), however, have long been suspected of possessing a significantly streamlined carbon metabolic network in which tricarboxylic acid metabolism plays a minor role. Blood-stage Plasmodium parasites rely almost entirely on glucose fermentation for energy and consume minimal amounts of oxygen, yet the parasite genome encodes all of the enzymes necessary for a complete tricarboxylic acid cycle. Here, by tracing (13)C-labelled compounds using mass spectrometry we show that tricarboxylic acid metabolism in the human malaria parasite Plasmodium falciparum is largely disconnected from glycolysis and is organized along a fundamentally different architecture from the canonical textbook pathway. We find that this pathway is not cyclic, but rather is a branched structure in which the major carbon sources are the amino acids glutamate and glutamine. As a consequence of this branched architecture, several reactions must run in the reverse of the standard direction, thereby generating two-carbon units in the form of acetyl-coenzyme A. We further show that glutamine-derived acetyl-coenzyme A is used for histone acetylation, whereas glucose-derived acetyl-coenzyme A is used to acetylate amino sugars. Thus, the parasite has evolved two independent production mechanisms for acetyl-coenzyme A with different biological functions. These results significantly clarify our understanding of the Plasmodium metabolic network and highlight the ability of altered variants of central carbon metabolism to arise in response to unique environments.

Indexed as

AcetylationAcetyl Coenzyme AAmino SugarsAnimalsCarbonCitric Acid CycleErythrocytesGlucoseGlutamic AcidGlutamineGlycolysisHistonesMalatesPlasmodium falciparumAcetyl Coenzyme AAmino SugarsCarbonGlucoseGlutamic AcidGlutamineHistonesMalatesmalic acid

Identifiers

PMID20686576
PMCPMC2917841
OpenAlexW2037573325

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.