Endogenous nitric oxide synthase inhibitors are responsible for the L‐arginine paradox
Abstract
L‐Arginine, the substrate of nitric oxide (NO) synthases (NOSs), is found in the mammalian organism at concentrations by far exceeding K M values of these enzymes. Therefore, additional L‐arginine should not enhance NO formation. In vivo, however, increasing L‐arginine concentration in plasma has been shown repeatedly to increase NO production. This phenomenon has been named the L‐arginine paradox; it has found no satisfactory explanation so far. In the present work, evidence for the hypothesis that the endogenous NOS inhibitors methylarginines, asymmetric dimethylarginine being the most powerful (IC 50 1.5 μM), are responsible for the L‐arginine paradox is presented.
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Mitochondrial enzymes beyond the ETC-pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and monoamine oxygenase A and B-have been reported to generate ROS.
“Pyruvate dehydrogenase (887), α-ketoglutarate dehydrogenase (130, 887, 952), and monoamine oxygenase A and B (290) have all been demonstrated to serve as ROS sources.”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [952]
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Self-citation
- Authors
- Tsikas, D., Böger, R. H., Sandmann, J., Bode-Böger, S. M., & Frölich, J. C.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2000-07-24
- Volume
- 478
- Issue
- 1-2
- Pages
- 1-3
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2000940740
- Cited by
- 237
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 9 · 2018: 4 · 2017: 11 · 2016: 3 · 2015: 16 · 2014: 6 · 2013: 10 · 2012: 11
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- nitric oxide synthase inhibitors, asymmetric dimethylarginine, methylarginines, nitric oxide production, L-arginine
- MeSH terms
- Animals, Arginine, Binding, Competitive, Enzyme Inhibitors, Humans, Kinetics, Models, Biological, Thermodynamics, Meta-Analysis as Topic, Nitric Oxide Synthase, omega-N-Methylarginine, Inhibitory Concentration 50, Rats
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