Evidence map›Paper›PMID 22069723›Full record

Trial reportToxins2011

4-Pyridone-3-carboxamide-1-β-D-ribonucleoside triphosphate (4PyTP), a novel NAD metabolite accumulating in erythrocytes of uremic children: a biomarker for a toxic NAD analogue in other tissues?

Elena Synesiou, Lynnette D Fairbanks, H Anne Simmonds, Ewa M Slominska, Ryszard T Smolenski, Elizabeth A Carrey

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in Toxins, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 29% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. The Biochemical Pathways of Nicotinamide-Derived Pyridones.International journal of molecular sciences · 2021
    Article
  9. Article
  10. Article
  11. The chemistry of the vitamin B3 metabolome.Biochemical Society transactions · 2019
    Review
  12. Review
  13. Observational
  14. 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

6 authors at 3 institutions in 2 countries.

Elena SynesiouUniversity College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Lynnette D Fairbanks
H Anne Simmonds
Ewa M Slominska
Ryszard T Smolenski
Elizabeth A Carrey
Gdańsk Medical University · PLSt Thomas' Hospital · GBUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have identified a novel nucleotide, 4-pyridone 3/5-carboxamide ribonucleoside triphosphate (4PyTP), which accumulates in human erythrocytes during renal failure. Using plasma and erythrocyte extracts obtained from children with chronic renal failure we show that the concentration of 4PyTP is increased, as well as other soluble NAD(+) metabolites (nicotinamide, N(1)-methylnicotinamide and 4Py-riboside) and the major nicotinamide metabolite N(1)-methyl-2-pyridone-5-carboxamide (2PY), with increasing degrees of renal failure. We noted that 2PY concentration was highest in the plasma of haemodialysis patients, while 4PyTP was highest in erythrocytes of children undergoing peritoneal dialysis: its concentration correlated closely with 4Py-riboside, an authentic precursor of 4PyTP, in the plasma. In the dialysis patients, GTP concentration was elevated: similar accumulation was noted previously, as a paradoxical effect in erythrocytes during treatment with immunosuppressants such as ribavirin and mycophenolate mofetil, which deplete GTP through inhibition of IMP dehydrogenase in nucleated cells such as lymphocytes. We predict that 4Py-riboside and 4Py-nucleotides bind to this enzyme and alter its activity. The enzymes that regenerate NAD(+) from nicotinamide riboside also convert the drugs tiazofurin and benzamide riboside into NAD(+) analogues that inhibit IMP dehydrogenase more effectively than the related ribosides: we therefore propose that the accumulation of 4PyTP in erythrocytes during renal failure is a marker for the accumulation of a related toxic NAD(+) analogue that inhibits IMP dehydrogenase in other cells.

Indexed as

AdolescentBiomarkersChildChromatography, High Pressure LiquidErythrocytesFemaleGlomerular Filtration RateHumansKidney Failure, ChronicMaleMass SpectrometryNADNucleotidesRenal DialysisSeverity of Illness IndexUremia4-pyridone-3-carboxamide N-1 riboside triphosphateBiomarkersNADNucleotides4-pyridone 3/5-carboxamide ribonucleoside triphosphate (4PyTP)erythrocytesHPLCIMP dehydrogenaseNAD+nicotinamide riboside (NR)pyridoneuremia

Identifiers

PMID22069723
PMCPMC3202843
OpenAlexW2040061117

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.