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Department of Animal Sciences and Division of Nutrition Sciences, University of Illinois, Urbana, IL 61801
* To whom correspondence should be addressed. E-mail: dhbaker{at}uiuc.edu.
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ABSTRACT |
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 TOP ABSTRACT LITERATURE CITED |
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Arginine
The articles that follow discuss functions, metabolism, pharmacokinetics, and clinical uses for supplemental arginine. Clearly, urea-cycle function and nitrogen elimination are crucial features in the functionality of arginine. Interspecies comparisons in the consequences of arginine deficiency are fascinating (4,5).
Feline species have very limited capacity to make citrulline in intestinal mucosal cells, and as a result, cats consuming only 1 meal of an arginine-free diet develop severe hyperammonemia and often die after only 24 h (5). In contrast, feeding chicks (zero in vivo arginine biosynthesis) an arginine-free diet, although resulting in negative growth, yields mortality only after 27 d of feeding (6). Young pigs do not grow optimally when fed a diet very low in arginine (7,8), but adult pigs, including gravid females, synthesize enough arginine (in kidney tissue) to meet their functional requirements (9,10). A classic study was done at UC-Davis in which an arginine-free diet was consumed by adult humans for 5 d (11). No symptoms of arginine deficiency occurred, and plasma ammonia and urinary orotic acid remained in the normal range. The results of this study suggest that normal healthy adults can synthesize enough arginine to meet minimal functional requirements.
Ball's laboratory in Alberta fed (using a gastric catheter) or provided IV an arginine- and proline-free diet to neonatal piglets (12). Whether they were fed enterally or parenterally, hyperammonemia rapidly occurred. However, providing proline in the arginine-free formula prevented the elevation of plasma ammonia, but only in the case of enterally fed piglets. These interesting findings demonstrate that the gut is vitally involved in the arginine-sparing effect of proline (13).
Antagonism of arginine by excess dietary lysine is of great interest in animal nutrition. Species differences exist in that antagonism occurs in chicks (14), rats (15), guinea pigs (16), and dogs (17) but not in pigs (18). This is of greatest practical significance in avian species because they have high arginine requirements, and excess lysine enhances arginine catabolism by inducing kidney arginase.
Arginine has become a prominent amino acid in several disease states, not only those related to nitric oxide (NO) production but also those associated with the arginine catabolic enzyme, arginase (19–21). Arginase is released from human red blood cells and is therefore a factor in hemolytic diseases such as sickle cell disease. Arginase activity is also elevated in asthmatic patients, possibly limiting the availability of arginine for NO biosynthesis. These topics are discussed in more detail in the articles that follow.
Lysine
Lysine could be viewed as the "forgotten" amino acid in human nutrition. This amino acid is rich in the food supply of developed countries. However, in poor countries where cereals dominate the food supply, lysine is the most limiting amino acid in the food supply. Based on rat studies, every cereal grain that has been studied is not only deficient but also 1st limiting in lysine (22). Lysine is also the most limiting amino acid in typical diets fed to pigs; it is second limiting after methionine in typical diets fed to avian species. Not surprisingly, therefore, well over 90% of the total lysine production is used to supplement animal diets. In 2005, 200,000 metric tons of lysine were used in the United States, alone, for animal feed applications (23). Thus, lysine has probably been studied more in animal nutrition than any other amino acid, but it has not received the same degree of emphasis in human nutrition. This is perhaps because few pharmacologic uses for lysine in the clinical setting have been advanced.
Topics dealt with in the articles that follow are 1) lysine metabolism and mitochondrial uptake (24), 2) susceptibility of lysine in both its free and protein-bound state to Maillard browning in foods and feeds exposed to high temperature and humidity (25,26), 3) susceptibility of lysine in foods under heat and alkaline conditions to loss of bioactivity as a result of lysinoalanine synthesis (27), 4) upper limit studies, including effects of lysine per se as well as effects of the HCl portion of lysine administered as L-lysine·HCl (18,28–31), 5) antagonism of arginine caused by excess lysine inducing kidney arginase in avian species (14,32), 6) use of lysine as a reference amino acid in diet formulation for animals based on the "ideal protein" (i.e., ideal amino acid ratios) concept (5,33–37), and 7) molecular genetic approaches to increasing the lysine content (both free and protein bound) in cereal grains and oil seeds (38,39).
In the articles that are included in this supplement, topics ancillary to but associated with lysine and arginine are discussed as well. These include metabolites of lysine such as saccharopine, 
-aminoadipic acid, -ketoadipic acid (also a metabolite of tryptophan), trimethyllysine, and carnitine as well as metabolites of arginine such as ornithine, citrulline, dimethylarginine, creatine, agmatine, polyamines, urea, and, of course, NO.
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FOOTNOTES |
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2 Author disclosures: D. H. Baker received travel support from ICAAS to attend the workshop.
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LITERATURE CITED |
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TOPABSTRACTLITERATURE CITED |
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1. Harris RA, Joshi M, Jeoung NH, Obayashi M. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. J Nutr. 2005;135:1527S–30S.[Medline]
2. Cynober L. Introduction to the 5th amino acid assessment workshop. J Nutr. 2006;136:1633S–5S.
3. Brosnan JT, Brosnan ME. The sulfur-containing amino acids: an overview. J Nutr. 2006;136:1636S–40S.
4. Morris JG, Rogers QR. Ammonia intoxication in the near-adult cat as a result of dietary deficiency of arginine. Science. 1978;199:431–2.
5. Ball RO, Urschel KL, Pencharz PB. Nutritional consequences of interspecies differences in arginine and lysine metabolism. J Nutr. 2007;137:1626S–41S.
6. Ousterhout LE. Survival time and biochemical changes in chicks fed diets lacking different essential amino acids. J Nutr. 1960;70:226–34.
7. Southern LL, Baker DH. Arginine requirement of the young pig. J Anim Sci. 1983;57:402–12.
8. Edmonds MS, Lowry KR, Baker DH. Urea-cycle metabolism: effects of supplemental ornithine or citrulline on performance, tissue amino acid concentrations and enzymatic activity in young pigs fed arginine-deficient diets. J Anim Sci. 1987;65:706–16.
9. Easter RA, Katz RS, Baker DH. Arginine: a dispensable amino acid for postpubertal growth and pregnancy of swine. J Anim Sci. 1974;39:1123–8.
10. Easter RA, Baker DH. Nitrogen metabolism and reproductive response of gravid swine fed an arginine-free diet during the last 84 days of gestation. J Nutr. 1976;106:636–41.
11. Carey GP, Kime Z, Rogers QR, Morris JG, Hargrove D, Buffington CA, Brusilow SW. An arginine-deficient diet in humans does not evoke hyperammonemia or orotic aciduria. J Nutr. 1987;117:1734–9.
12. Brunton JA, Bertolo RFP, Pencharz PB, Ball RO. Proline ameliorates arginine deficiency during enteral but not parenteral feeding in neonatal piglets. Am J Physiol. 1999;277:E223–31.[Medline]
13. Flynn NE, Wu G. An important role for endogenous synthesis of arginine in maintaining arginine homeostatis in neonatal pigs. Am J Physiol. 1996;271:R1149–55.[Medline]
14. Austic RE, Scott RL. Involvement of food intake in the lysine-arginine antagonism in chicks. J Nutr. 1975;105:1122–31.
15. Ulman EA, Kari FW, Hevia P, Visek W. Orotic aciduria caused by feeding excess lysine to growing rats. J Nutr. 1981;111:1772–9.
16. O'Dell BL, Amos WH, Savage JE. Relation of chick kidney arginase to growth rate and dietary arginine. Proc Soc Exp Biol Med. 1965;118:102–5.[Medline]
17. Czarnecki GL, Hirakawa DA, Baker DH. Antagonism of arginine by excess dietary lysine in the growing dog. J Nutr. 1985;115:743–52.
18. Edmonds MS, Baker DH. Failure of excess dietary lysine to antagonize arginine in young pigs. J Nutr. 1987;117:1396–401.
19. Morris SM. Arginine metabolism in vascular biology and disease. Vasc Med. 2005;10:S83–7.
20. Morris SM. Arginine: beyond protein. Am J Clin Nutr. 2006;83:508S–12S.
21. Wu G, Morris SM. Arginine metabolism: nitric oxide and beyond. Biochem J. 1998;336:1–17.[Medline]
22. Howe EE, Jansen GR, Gilfillan EW. Amino acid supplementation of cereal grains as related to the world food supply. Am J Clin Nutr. 1965;16:315–20.[Abstract]
23. Anonymous. Strategic analysis of the U.S. market for amino acids. Frost and Sullivan Report F475–88 2006; 220 pp.
24. Benevenga NJ, Blemings KP. Unique aspects of lysine nutrition and metabolism. J Nutr. 2007;137:1610S–15S.
25. Adrian J. Nutritional and physiological consequences of the Maillard reaction. World Rev Nutr Diet. 1974;19:71–122.[Medline]
26. Robbins KR, Baker DH. Evaluation of the resistance of lysine sulfite to Maillard destruction. J Agric Food Chem. 1980;28:25–9.[Medline]
27. Robbins KR, Baker DH, Finley JW. Studies on the utilization of lysinoalanine and lanthionine. J Nutr. 1980;110:907–15.
28. Edmonds MS, Gonyou HW, Baker DH. Effect of excess levels of methionine, tryptophan, arginine, lysine or threonine on growth and dietary choice in the pig. J Anim Sci. 1987;65:179–85.
29. Edmonds MS, Baker DH. Comparative effects of individual amino acid excesses when added to a corn-soybean meal diet: effects on growth and dietary choice in the chick. J Anim Sci. 1987;65:699–705.
30. Sauberlich HE. Studies on the toxicity and antagonism of amino acids for weanling rats. J Nutr. 1961;75:61–72.
31. Harper AE, Benevenga NJ, Wohlhueter RM. Effects of ingestion of disproportionate amounts of amino acids. Physiol Rev. 1970;50:428–558.
32. Allen NK, Baker DH. Effect of excess lysine on the utilization of and requirement for arginine by the chick. Poult Sci. 1972;51:902–6.[Medline]
33. Wang TC, Fuller MF. The optimum dietary amino acid pattern for growing pigs. 1. Experiments by amino acid deletion. Br J Nutr. 1989;62:77–89.[Medline]
34. Chung TK, Baker DH. Ideal amino acid pattern for 10-kilogram pigs. J Anim Sci. 1992;70:3102–11.[Abstract]
35. Baker DH, Han Y. Ideal amino acid profile for broiler chicks during the first three weeks posthatching. Poult Sci. 1994;73:1441–7.[Medline]
36. Heger J, Van Phung T, Krizova L. Efficiency of amino acid utilization in the growing pig at suboptimal levels of intake: lysine, threonine, sulphur amino acids, and tryptophan. J Anim Physiol Anim Nutr (Berl). 2002;86:153–65.[Medline]
37. Baker DH. Tolerance for branched-chain amino acids in experimental animals and humans. J Nutr. 2005;135:1585S–90S.
38. Sun SSM, Qiaoquan L. Transgenic approaches to improve the nutritional quality of plant proteins. In Vitro Cell Dev Biol Plant. 2004;40:155–62.
39. Mandal S, Mandal RK. Seed storage proteins and approaches for improvement of their nutritional quality by genetic engineering. Curr Sci. 2000;79:576–89.
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