Effect of caffeine on metabolism of L-arginine in the brain

Mol Cell Biochem. 2003 Feb;244(1-2):125-8.


Methylxanthines are widely consumed because of their stimulating effect primarily on the central nervous system. Their diuretic and respiratory stimulant action is used in clinical medicine. L-Arginine metabolism in the brain is very important for normal brain function. In addition to brain protein synthesis, arginine is a substrate for the production of urea, creatine, nitric oxide, agmatine, glutamic acid, ornithine, proline and polyamines. As known, many of these compounds are very important in brain function. There is no information relating to effects of caffeine on arginine metabolism in the brain, however, there is a lot of new information about arginine metabolism and caffeine action on the central nervous system. So, we have hypothesized the existence of a relationship that may be of interest in understanding mechanisms of caffeine effects on the central nervous system that may have utility in the clinical applications. In our experiment protocol we used male Wistar rats weighing about 200 g. Caffeine was added to the drinking water in gradually increasing amounts, from 2 g/l over the first 3 days, to 4 g/l over the last 7 days. A control group was given drinking water without caffeine. The level of lipid peroxidation, arginase and diamine oxidase (DAO) activity in the brain was measured. The results of our study show that arginase and diamine oxidase were decreased in animals treated with caffeine. The level of lipid peroxidation (MDA) was decreased also. The inhibitory effect of caffeine on arginase activity indicates that caffeine provides more arginine for consumption in other metabolic pathways. Considering the central stimulant effects of caffeine and the decreased lipid peroxidation level, it can be assumed that moderate short-term consumption of caffeine may be beneficial for brain function.

MeSH terms

  • Amine Oxidase (Copper-Containing) / metabolism
  • Animals
  • Arginase / metabolism
  • Arginine / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism*
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Creatine / blood
  • Humans
  • Lipid Peroxidation
  • Male
  • Malondialdehyde / blood
  • Polyamines / metabolism
  • Rats
  • Rats, Wistar
  • Urea / blood
  • Uric Acid / blood


  • Central Nervous System Stimulants
  • Polyamines
  • Uric Acid
  • Caffeine
  • Malondialdehyde
  • Urea
  • Arginine
  • Amine Oxidase (Copper-Containing)
  • Arginase
  • Creatine