Evidence map›Paper›PMID 19328848›Full record

ArticleFree radical biology & medicine2009

Inhibition of nitric oxide synthase by cobalamins and cobinamides.

J Brice Weinberg, Youwei Chen, Ning Jiang, Bethany E Beasley, John C Salerno, Dipak K Ghosh

Erratum issued Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Free radical biology & medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT03783091 (A Phase II Double Blind Randomized Controlled Trial of High Dose Vitamin B12 in Septic Shock), which is not on this map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 21% 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.

NCT03783091 phase2completednot on this mapstarted 2019, after this paper: background citation

A Phase II Double Blind Randomized Controlled Trial of High Dose Vitamin B12 in Septic Shock

TypeinterventionalSponsorMedical College of WisconsinRan2019 to 2023Enrolled20ConditionsSeptic ShockArmsHydroxocobalamin, Placebo
3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Efficacy of Treating Nifedipine-Induced Shock with Hydroxocobalamin in a Swine Model.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Observational
  8. Comment on: "Methylene Blue-Induced Serotonin Toxicity: Case Files of the Medical Toxicology Fellowship at the New York City Poison Control Center".Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Vitamin therapy in sepsis.Pediatric research · 2022
    Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

J Brice WeinbergDivision of Hematology-Oncology, Department of Medicine, Duke University and V.A. Medical Centers, Durham, NC 27705, USA. brice@duke.edu
Youwei Chen
Ning Jiang
Bethany E Beasley
John C Salerno
Dipak K Ghosh
Duke Medical Center · USKennesaw State University · US

Funding

NITRIC OXIDE AND SEVERE MALARIAR01AI041764 · NIAID · DUKE UNIVERSITY · PI WEINBERG, JOE BRICE · 1997 to 2012
$6.3M
Inducible NOS as a Treatment Target in CLLR01CA090548 · NCI · DUKE UNIVERSITY · PI WEINBERG, JOE BRICE · 2001 to 2005
$1.3M
NCI NIH HHS R01 CA090548NIAID NIH HHS R01 AI041764
6 · The paper itself

Abstract

Cobalamins are important cofactors for methionine synthase and methylmalonyl-CoA mutase. Certain corrins also bind nitric oxide (NO), quenching its bioactivity. To determine if corrins would inhibit NO synthase (NOS), we measured their effects on -L-[(14)C]arginine-to-L-[(14)C]citrulline conversion by NOS1, NOS2, and NOS3. Hydroxocobalamin (OH-Cbl), cobinamide, and dicyanocobinamide (CN(2)-Cbi) potently inhibited all isoforms, whereas cyanocobalamin, methylcobalamin, and adenosylcobalamin had much less effect. OH-Cbl and CN(2)-Cbi prevented binding of the oxygen analog carbon monoxide (CO) to the reduced NOS1 and NOS2 heme active site. CN(2)-Cbi did not react directly with NO or CO. Spectral perturbation analysis showed that CN(2)-Cbi interacted directly with the purified NOS1 oxygenase domain. NOS inhibition by corrins was rapid and not reversed by dialysis with L-arginine or tetrahydrobiopterin. Molecular modeling indicated that corrins could access the unusually large heme- and substrate-binding pocket of NOS. Best fits were obtained in the "base-off" conformation of the lower axial dimethylbenzimidazole ligand. CN(2)-Cbi inhibited interferon-gamma-activated Raw264.7 mouse macrophage NO production. We show for the first time that certain corrins directly inhibit NOS, suggesting that these agents (or their derivatives) may have pharmacological utility. Endogenous cobalamins and cobinamides might play important roles in regulating NOS activity under normal and pathological conditions.

Indexed as

AnimalsCattleCobamidesDose-Response Relationship, DrugHumansMacrophagesMiceModels, MolecularNitric OxideNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRatsRecombinant ProteinsStructure-Activity RelationshipVitamin B 12CobamidescobinamideNitric OxideNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIIRecombinant ProteinsVitamin B 12

Identifiers

PMID19328848
PMCPMC2745708
OpenAlexW2010379106

What OpenQuestion holds

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Registered trials

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.