Evidence map›Paper›PMID 17934141›Full record

ArticleDiabetes2008

Inactivation of glyceraldehyde-3-phosphate dehydrogenase by fumarate in diabetes: formation of S-(2-succinyl)cysteine, a novel chemical modification of protein and possible biomarker of mitochondrial stress.

Matthew Blatnik, Norma Frizzell, Suzanne R Thorpe, John W Baynes

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

Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 12% 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

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.

  1. Pooled it
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  16. Metabolite itaconate in host immunoregulation and defense.Cellular & molecular biology letters · 2023
    Review
  17. Article
  18. Mitochondrial stress and glycoxidation increase with decreased kidney function.Journal of clinical biochemistry and nutrition · 2023
    Article
  19. Article
  20. Review

15 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

4 authors at 1 institution in 1 country.

Matthew BlatnikDepartment of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA.
Norma Frizzell
Suzanne R Thorpe
John W Baynes
University of South Carolina · US

Funding

GLYCATION OF PROTEINS IN DIABETESR37DK019971 · NIDDK · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI BAYNES, JOHN WILLIAM · 1986 to 2010
$3.6M
GLYCATION OF PROTEIN IN DIABETESR01DK019971 · NIDDK · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI BAYNES, JOHN W · 1994 to 1994
–
NIDDK NIH HHS DK-19971NIDDK NIH HHS R37 DK019971
6 · The paper itself

Abstract

objectives(2-succinyl)cysteine (2SC) is formed by a Michael addition reaction of the Krebs cycle intermediate, fumarate, with cysteine residues in protein. We investigated the role of fumarate in chemical modification and inhibition of the sulfhydryl enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in vitro and in tissues of diabetic rats. RESEARCH DESIGN AND

methodsGAPDH was incubated with fumarate in PBS to assess effects of fumarate on enzyme activity in vitro. Sites of 2SC formation were determined by analysis of tryptic peptides by high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry. 2SC and fumarate in gastrocnemius muscle of control and streptozotocin-induced diabetic rats were measured by liquid chromatography/tandem mass spectrometry and by gas chromatography/mass spectrometry, respectively. GAPDH was isolated from muscle by immunoprecipitation, and sites of modification of GAPDH were determined by mass spectrometry analysis.

results2SC was found, both in vitro and in vivo, about equally at active-site Cys-149 and nucleophilic Cys-244. Inactivation of GAPDH by fumarate in vitro correlated with formation of 2SC. In diabetic compared with control rats, fumarate and 2SC concentration increased approximately fivefold, accompanied by an approximately 25% decrease in GAPDH specific activity. The fractional modification of GAPDH by 2SC was significantly increased in diabetic versus control animals, consistent with the decreased specific activity of GAPDH in muscle of diabetic animals.

conclusionsFumarate contributes to inactivation of GAPDH in diabetes. 2SC may be a useful biomarker of mitochondrial stress in diabetes. Modification of GAPDH and other enzymes and proteins by fumarate may contribute to the metabolic changes underlying the development of diabetes complications.

Indexed as

AnimalsChromatography, LiquidCysteineDiabetes Mellitus, ExperimentalFumaratesGas Chromatography-Mass SpectrometryGlyceraldehyde 3-Phosphate Dehydrogenase (NADP+)KineticsMass SpectrometryMitochondriaMuscle, SkeletalPeptide FragmentsRatsCysteineFumaratesGlyceraldehyde 3-Phosphate Dehydrogenase (NADP+)Peptide FragmentsS-(2-succinyl)cysteine

Identifiers

PMID17934141
PMCPMC2423377
OpenAlexW2169812410

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.