Nitric oxide metabolism and breakdown
Open accessAbstract
The steady-state concentration and thus the biological effects of NO are critically determined not only by its rate of formation, but also by its rate of decomposition. Bioreactivity of NO at physiological concentrations may differ substantially from that suggested by in vitro experiments. The charge neutrality and its high diffusion capacity are hallmarks that characterize NO bioactivity. Reactive oxygen derived species are major determinants of NO breakdown. Biotransformation of NO and its related N-oxides occurs via different metabolic routes within the body. S-Nitrosothiols formed upon reaction of NO with redox-activated thiols represent an active storage pool for NO. The major oxidative metabolites represent nitrite and nitrate, the ratio of both is determined by the microenvironmental redox conditions. In humans, circulating nitrite represents an attractive estimate of regional endothelial NO formation, whereas nitrate, with some caution, appears useful in estimating overall nitrogen/NO turnover. Within the near future, more specific biochemical tools for diagnosis of reduced NO bioactivity will become available. Increasing knowledge on the complex metabolism of NO in vivo will lead to the development of new therapeutic strategies to enhance bioactivity of NO via modulation of its metabolism.
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The half-time for NO is dependent upon pH, tissue oxygenation and the availability of nitrate.
“the half-time for NO is dependent upon pH, tissue oxygenation and the availability of nitrate (Kelm 1999)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Kelm 1999
Inorganic nitrate may lower blood pressure through greater nitric oxide production.
“The BP-lowering effects of inorganic nitrate may derive from increased generation of nitric oxide (NO) (13,14), a pleiotropic molecule involved in the vasodilation of large arteries and resistance vessels (13,14).”
From Inorganic Nitrate and Beetroot Juice Supplementation Reduces Blood Pressure in Adults: A Systematic Review and Meta-Analysis (2013) · cites this paper as [14]
The half-life of exogenously administered nitrite can range between 20-30 minutes.
“Earlier studies reported the half-life of NO2- in blood to be approximately 110 seconds; however, it is now clear that the half life of exogenously administered nitrite can range between 20–30 minutes thus making it a readily available buffering metabolite to maintain NO bioavailability [52, 68, 69].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [68]
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References 127 · Cited by 673
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- Authors
- Kelm, M.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Kelm, Malte
- ORCID
- Kelm, Malte
- Venue
- Biochimica et Biophysica Acta (BBA) - Bioenergetics
- Publisher
- Elsevier BV
- Published
- 1999-05
- Volume
- 1411
- Issue
- 2-3
- Pages
- 273-289
- ISSN
- 0005-2728 (ISSN-L)
- OpenAlex
- W2092175186
- Cited by
- 673
- References
- 127
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 26 · 2023: 23 · 2022: 32 · 2021: 31 · 2020: 35 · 2019: 29 · 2018: 41 · 2017: 39 · 2016: 34 · 2015: 36 · 2014: 14 · 2013: 15 · 2012: 24
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Bioenergetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- nitric oxide metabolism, reactive oxygen species, N-oxides, S-nitrosothiols, nitrite, nitrate, redox conditions, nitrogen turnover
- MeSH terms
- Animals, Circadian Rhythm, Digestive System, Endothelium, Vascular, Humans, Mercaptoethanol, Nitrates, Nitric Oxide, Nitrites, Nitrogen, Nitrogen Isotopes, Nitroso Compounds, Oxidation-Reduction, Respiratory System, Reactive Oxygen Species, S-Nitrosothiols
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