Chronic arginine intake is believed to have favorable effects on the body. However, it might be hypothesized that excessive consumption of an individual amino acid exerts adverse effects on distribution and metabolism of other amino acids. We evaluated the effect of chronic intake of arginine on amino acid concentrations in blood plasma, liver, kidneys, and soleus and extensor digitorum longus muscles. Rats were fed a standard diet or a high-arginine diet (HAD) for two months. Half of the animals in each group were sacrificed in the fed state, and the other half after fasting overnight. HAD increased blood plasma concentrations of urea, creatinine, arginine, and ornithine and decreased most other amino acids. Arginine and ornithine also increased in muscles and kidneys; an increase of lysine was observed in both muscle types. Methionine, phenylalanine, threonine, asparagine, glycine, serine, and taurine decreased in most tissues of HAD fed animals. Most of the effects of HAD disappeared after overnight fasting. It is concluded that (i) enhanced dietary arginine intake alters distribution of almost all amino acids; and (ii) to attain a better assessment of the effects of various nutritional interventions, an appropriate number of biochemical measurements must be performed in both postprandial and postabsorptive states.

Department of Physiology Charles University Prague Faculty of Medicine in Hradec Kralove Hradec Kralove 500 38 Czech Republic

Zobrazit více v PubMed

Morris S.M. Arginine: Beyond protein. Am. J. Clin. Nutr. 2006;83:508S–512S. PubMed

Das U.N., Repossi G., Dain A., Eynard A.R. l-arginine, NO and asymmetrical dimethylarginine in hypertension and type 2 diabetes. Front. Biosci. 2011;16:13–20. doi: 10.2741/3672. PubMed DOI

Zhou M., Martindale R.G. Arginine in the critical care setting. J. Nutr. 2007;137:1687S–1692S. PubMed

Barbul A., Sisto D.A., Wasserkrug H.L., Efron G. Arginine stimulates lymphocyte immune response in healthy human beings. Surgery. 1981;90:244–251. PubMed

Evans R.W., Fernstrom J.D., Thompson J., Morris S.M., Kuller L.H. Biochemical responses of healthy subjects during dietary supplementation with l-arginine. J. Nutr. Biochem. 2004;15:534–539. doi: 10.1016/j.jnutbio.2004.03.005. PubMed DOI

Bergström J., Fürst P., Norée L.O., Vinnars E. Intracellular free amino acid concentration in human muscle tissue. J. Appl. Physiol. 1974;36:693–697. PubMed

Graham J.A., Lamb J.F., Linton A.L. Measurement of body water and intracellular electrolytes by means of muscle biopsy. Lancet. 1976;2:1172–1176. doi: 10.1016/S0140-6736(67)91892-2. PubMed DOI

Xiong Y., Fru M.F., Yu Y., Montani J.P., Ming X.F., Yang Z. Long term exposure to l-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling. Aging. 2014;6:369–379. doi: 10.18632/aging.100663. PubMed DOI PMC

Rabier D., Kamoun P. Metabolism of citrulline in man. Amino Acids. 1995;9:299–316. doi: 10.1007/BF00807268. PubMed DOI

Li H., Meininger C.J., Hawker J.R., Haynes T.E., Kepka-Lenhart D., Mistry S.K., Morris S.M., Wu G. Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells. Am. J. Physiol. Endocrinol. Metab. 2001;280:E75–E82. PubMed

Holecek M., Kovarik M. Alterations in protein metabolism and amino acid concentrations in rats fed by a high-protein (casein-enriched) diet—Effect of starvation. Food Chem. Toxicol. 2011;49:3336–3342. doi: 10.1016/j.fct.2011.09.016. PubMed DOI

Christensen H.N. Role of amino acid transport and countertransport in nutrition and metabolism. Physiol. Rev. 1990;70:43–77. PubMed

Kovarik M., Muthny T., Sispera L., Holecek M. The dose-dependent effects of endotoxin on protein metabolism in two types of rat skeletal muscle. J. Physiol. Biochem. 2012;68:385–395. doi: 10.1007/s13105-012-0150-6. PubMed DOI

Holecek M., Sispera L. Glutamine deficiency in extracellular fluid exerts adverse effects on protein and amino acid metabolism in skeletal muscle of healthy, laparotomized, and septic rats. Amino Acids. 2014;46:1377–1384. doi: 10.1007/s00726-014-1701-7. PubMed DOI

Holecek M., Kandar R., Sispera L., Kovarik M. Acute hyperammonemia activates branched-chain amino acid catabolism and decreases their extracellular concentrations: Different sensitivity of red and white muscle. Amino Acids. 2011;40:575–584. doi: 10.1007/s00726-010-0679-z. PubMed DOI

Holecek M., Sispera L., Skalska H. Enhanced glutamine availability exerts different effects on protein and amino acid metabolism in skeletal muscle from healthy and septic rats. J. Parenter. Enter. Nutr. 2015;39:847–854. doi: 10.1177/0148607114537832. PubMed DOI

Flodin N.W. The metabolic roles, pharmacology, and toxicology of lysine. J. Am. Coll. Nutr. 1997;16:7–21. doi: 10.1080/07315724.1997.10718644. PubMed DOI

Bergström J., Fürst P., Vinnars E. Effect of a test meal, without and with protein, on muscle and plasma free amino acids. Clin. Sci. 1990;79:331–337. doi: 10.1042/cs0790331. PubMed DOI

Bushinsky D.A., Gennari F.J. Life-threatening hyperkalemia induced by arginine. Ann. Intern. Med. 1978;89:632–634. doi: 10.7326/0003-4819-89-5-632. PubMed DOI

Barron J.L., Klaff L.J., Levitt N.S., Ling N., Millar R.P. Arginine hydrochloride stimulation of serum potassium and aldosterone is enhanced by somatostatin-28. Acta Endocrinol. 1984;105:407–410. doi: 10.1530/acta.0.1050407. PubMed DOI

Whang R., Papper S., Llach F. Arginine-induced hypermagnesemia and hyperkalemia in nephrectomized rats. Magnesium. 1988;7:23–26. PubMed

Schulze F., Glos S., Petruschka D., Altenburg C., Maas R., Benndorf R., Schwedhelm E., Beil U., Böger R.H. l-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. Nutr. Res. 2009;29:291–297. doi: 10.1016/j.nutres.2009.04.004. PubMed DOI

Yang Y., Wu Z., Jia S., Dahanayaka S., Feng S., Meininger C.J., McNeal C.J., Wu G. Safety of long-term dietary supplementation with l-arginine in rats. Amino Acids. 2015;47:1909–1920. doi: 10.1007/s00726-015-1992-3. PubMed DOI

Aspartic Acid in Health and Disease

Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver

Side effects of amino acid supplements