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

FEBS Lett. 2000 Jul 28;478(1-2):1-3. doi: 10.1016/s0014-5793(00)01686-0.


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 microM), are responsible for the L-arginine paradox is presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arginine / metabolism
  • Arginine / pharmacology*
  • Binding, Competitive
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Meta-Analysis as Topic
  • Models, Biological*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Thermodynamics
  • omega-N-Methylarginine / blood
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • omega-N-Methylarginine
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase