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Cited by 285Hemoglobin structure and functionNitric Oxide and Endothelin EffectsHeme Oxygenase-1 and Carbon Monoxide

Nitrosative stress: Metabolic pathway involving the flavohemoglobin

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Hausladen, Alfred, Gow, Andrew J., Stamler, Jonathan S.·1998·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.95.24.14100PMC PMC24333
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Abstract

Nitric oxide (NO) biology has focused on the tightly regulated enzymatic mechanism that transforms l -arginine into a family of molecules, which serve both signaling and defense functions. However, very little is known of the pathways that metabolize these molecules or turn off the signals. The paradigm is well exemplified in bacteria where S -nitrosothiols (SNO)—compounds identified with antimicrobial activities of NO synthase—elicit responses that mediate bacterial resistance by unknown mechanisms. Here we show that Escherichia coli possess both constitutive and inducible elements for SNO metabolism. Constitutive enzyme(s) cleave SNO to NO whereas bacterial hemoglobin, a widely distributed flavohemoglobin of poorly understood function, is central to the inducible response. Remarkably, the protein has evolved a novel heme-detoxification mechanism for NO. Specifically, the heme serves a dioxygenase function that produces mainly nitrate. These studies thus provide new insights into SNO and NO metabolism and identify enzymes with reactions that were thought to occur only by chemical means. Our results also emphasize that the reactions of SNO and NO with hemoglobins are evolutionary conserved, but have been adapted for cell-specific function.

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  • Higher NO concentrations (>1 μM) can lead to oxidative stress and nitrative and nitrosative stress via peroxynitrite and nitrosating species, and in combination with oxygen can trigger posttranslational modification of proteins, lipids, and DNA.

    “Higher concentrations of NO (>1 μM) can lead not only to oxidative stress but also nitrative and nitrosative stress via the generation of peroxynitrite and nitrosating species”

    From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [411]

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Authors
Hausladen, A., Gow, A. J., & Stamler, J. S.
Affiliations
Howard Hughes Medical Institute (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1998-11-24
Volume
95
Issue
24
Pages
14100-14105
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.95.24.14100
PMC
PMC24333
OpenAlex
W2069848230
Cited by
285
References
37
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 7 · 2017: 2 · 2016: 7 · 2015: 4 · 2014: 10 · 2013: 13 · 2012: 17
FWCI
5.88
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01hl052529-05)
  • National Heart, Lung, and Blood Institute (HL 52529, R01HL059130, HL 59130)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
nitrosative stress, flavohemoglobin, nitric oxide metabolism, S-nitrosothiols, Escherichia coli, nitrate formation, bacterial hemoglobin, nitric oxide detoxification
MeSH terms
Cysteine, Diethylamines, Enzyme Inhibitors, Escherichia coli, Biological Evolution, Heme, Hemeproteins, Kinetics, Nitric Oxide, Nitrogen Oxides, Nitroso Compounds, Spectrophotometry, Tryptophan Oxygenase, Signal Transduction, S-Nitrosothiols

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