Whole-body synthesis of L-homoarginine in pigs and rats supplemented with L-arginine

Amino Acids. 2016 Apr;48(4):993-1001. doi: 10.1007/s00726-015-2145-4. Epub 2015 Dec 16.


Recent studies suggest an important role for L-homoarginine in cardiovascular, hepatic and neurological functions, as well as the regulation of glucose metabolism. However, little is known about whole-body L-homoarginine synthesis or its response to dietary L-arginine intake in animals. Four series of experiments were conducted to determine L-homoarginine synthesis and catabolism in pigs and rats. In Experiment 1, male and female pigs were fed a corn- and soybean meal-based diet supplemented with 0.0-2.42 % L-arginine-HCl. In Experiment 2, male and female rats were fed a casein-based diet, while receiving drinking water containing supplemental L-arginine-HCl to provide 0.0-3.6 g L-arginine/kg body-weight/day. In both experiments, urine collected from the animals for 24 h was analyzed for L-homoarginine and related metabolites. In Experiment 3, pigs and rats received a single oral dose of 1 or 10 mg L-homoarginine/kg body-weight, respectively, and their urine was collected for 24 h for analyses of L-homoarginine and related substances. In Experiment 4, slices of pig and rat tissues (including liver, brain, kidney, heart, and skeletal-muscle) were incubated for 1 h in Krebs-bicarbonate buffer containing 5 or 50 µM L-homoarginine. Our results indicated that: (a) animal tissues did not degrade L-homoarginine in the presence of physiological concentrations of other amino-acids; (b) 95-96 % of orally administered L-homoarginine was recovered in urine; (c) L-homoarginine was quantitatively a minor product of L-arginineg catabolism in the body; and (d) dietary L-arginine supplementation dose-dependently increased whole-body L-homoarginine synthesis. These novel findings provide a new framework for future studies of L-homoarginine metabolism and physiology in animals and humans.

Keywords: Animals; Arginine; Homoarginine; Metabolism; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animals
  • Arginine / administration & dosage
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Arginine / metabolism*
  • Arginine / urine
  • Body Weight / drug effects
  • Creatinine / urine
  • Dietary Supplements*
  • Female
  • Homoarginine / administration & dosage
  • Homoarginine / biosynthesis*
  • Homoarginine / urine
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Soybeans / chemistry
  • Swine
  • Zea mays / chemistry
  • omega-N-Methylarginine / blood
  • omega-N-Methylarginine / urine


  • Homoarginine
  • omega-N-Methylarginine
  • symmetric dimethylarginine
  • N,N-dimethylarginine
  • Arginine
  • Creatinine