Cited by 237Nitric Oxide and Endothelin EffectsCancer-related gene regulationAmino Acid Enzymes and Metabolism

Endogenous nitric oxide synthase inhibitors are responsible for the L‐arginine paradox

Tsikas, Dimitrios, Böger, Rainer H, Sandmann, Jörg, Bode-Böger, Stefanie M, Frölich, Jürgen C·2000·FEBS Letters

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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Crossref · 10.1016/s0014-5793(00)01686-0

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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.”

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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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