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Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801
2 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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KEY WORDS: • excess amino acids • cysteine • arginine • pigs • chickens
This review focuses on amino acid (AA)3 responses in experimental animals, primarily pigs and chickens, with emphasis on outcomes of excessive intake levels of single indispensable AAs in animals fed normal diets. The ideal protein concept (i.e., ideal AA ratios relative to Lys) has been well accepted in diet formulation schemes for both growing pigs (1–5) and chickens (3,6–9). Also, the 1998 National Research Council Subcommittee on Swine Nutrition (4) presented estimates of ideal AA ratios for protein accretion per se and maintenance per se based on work from the laboratories of Fuller (1) and Baker and colleagues (2,3,5,10–13). The most striking differences between ideal ratios (i.e., percent of Lys need) for maintenance and protein accretion occur with sulfur AAs (SAAs, i.e., Met plus Cys), Thr, and Arg. Thus the proposed Thr:Lys and SAA:Lys ideal ratios for maintenance per se are over twice as high as those for protein accretion per se. For Arg, where in vivo biosynthesis occurs (in mammals), the ideal ratio for accretion is 0.48, whereas for maintenance, it is less than zero. All these dietary ideal ratio estimates for pigs are based on (true) digestible levels of AAs present in a diet.
AA responses in growing animals support the view that crystalline AAs are essentially 100% digestible, i.e., absorbed (14,15), and also that there are inefficiencies in the use of absorbed AAs for protein accretion. Hence, recovery of absorbed AAs in whole-body protein when the level of a given AA is at a growth-limiting level is 80% or less (16–23). This is surprising, but even more vexing are findings that maintenance-requirement estimates based on zero protein accretion are meaningfully lower than those based on zero accretion of the AA under investigation. Indeed, animal studies suggest that at zero protein (or nitrogen) balance, dispensable AAs are in positive balance but indispensable AAs are in negative balance.
This review focuses on tolerances for excess AAs in pigs and chickens. Much of the literature on excess AAs in rats has involved specialized diets that are either low in protein or deficient in one or more AA. Also, pigs and chickens do not practice coprophagy, which is a potential confounding factor in assessment of untoward effects of excess AAs. Thus, studies involving pigs and chicks fed standard diets that contain all AAs at or in excess of requirements are emphasized.
Pig studies
The four bioassays from pigs reviewed in Table 1 (24,25) involved graded additions of DL-Met, L-Thr, or L-Leu to a standard corn–soybean meal (SBM) diet containing 196 g of crude protein (CP)/kg; the Lys trial, however, employed a semipurified diet (142 g of CP/kg) that contained Lys at its required level (11.5 g of Lys/kg). The corn-SBM diet contained SAAs and Thr at levels only slightly in excess of their requirements; Leu was present at 170% of its required level. These studies and others (24–26) suggest that excess Met (followed by Trp) is the most growth depressing among the indispensable AAs when plethoric dose levels are added to the diet. Lys, Thr, and Leu, in contrast, are much better tolerated when excess levels are fed. Relative to its baseline (i.e., normal) level in the plasma, Met accumulates to the greatest extent when excess Met is fed, which is perhaps an indication that the capacity of the transsulfuration pathway to metabolize Met has been exceeded. Thr also accumulates in plasma to a significant extent, although it was not growth depressing when fed at a great excess.
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-aminoadipic acid (25). At 34.5 g/kg of excess Lys, Lys, -aminoadipate, and all the basic AAs spill into the urine in considerable quantity. In fact, urinary Lys excretion accounted for 26% of the Lys intake when 34.5 g/kg of excess Lys was fed. The highest level of supplemental Lys shown in Table 1 (i.e., 34.5 g/kg) did not result in any significant changes in liver, kidney, or gut mucosal arginase or ornithine transcarbamoylase activity (25). Thus, excess Lys in the pig did not antagonize Arg. Avian studies
Studies on chickens with excess indispensable AAs added to standard corn-SBM diets (27–29) indicate that both growing chicks and adult laying hens have considerable tolerance for DL-Met and L-Lys even when the Lys is furnished as L-Lys·HCl. Dietary addition of 10 g/kg of excess DL-Met or L-Lys·HCl does not affect the growth rate of chicks (27) or the feed intake and egg production of layers (29). Large excesses (40 g/kg) of indispensable AAs, however, have variable effects on chick performance (Table 2). With plethoric dosing at 40 g/kg, Met, Phe, and Trp are very growth depressing, and the same level of excess Lys (as the acetate salt) is considerably more growth depressing in chicks than in pigs. Conversely, excess Arg is more growth depressing in pigs than in chicks (26,28). In chicks, excess Lys antagonizes Arg (30,31); anorexia, induction of kidney arginase, inhibition of hepatic glycine transamidinase, and urinary spillage of both Lys and Arg are all involved in the outcome of feeding excess dietary Lys to chicks. Growing dogs likewise show evidence of Lys-Arg antagonism when a large excess of Lys (40 g/kg) is fed (32).
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Excess AA mixtures
It is well to remember that any diet that has one or more AA at a deficient level also has an excess AA mixture over and above the AA deficiency. Moreover, protein sources considered near ideal (e.g., lactalbumin, egg albumin) have excess AAs. Egg albumin, for example, contains Ile at a level that is almost double that considered optimal for growing chicks and rats. Sugahara et al. (41) used crystalline AA diets to study single (and equal) indispensable AA deficiencies versus a deficiency of all indispensable AAs simultaneously in young chicks. Individual deficiencies (60% of requirement) of SAAs, Leu, Lys, and Arg resulted in growth rates superior to deficiencies (60% of requirement) of all AAs, but similar individual deficiencies of Phe plus Tyr, Trp, or Ile produced growth rates inferior to the diet that was deficient in all AAs. The growth responses noted were due almost entirely to differences in voluntary food intake. With the balanced total deficiency, food intake was not reduced relative to the positive control (all AAs at 100% of requirement), but all the individual deficiencies caused a reduction in voluntary food intake with the greatest reductions occurring when Phe plus Tyr, Trp, or Ile were singly deficient. Remarkably, relative to the total AA deficiency, none of the individual deficiencies reduced the gain:food ratio. This indicates that at the levels of excess AA involved (i.e., mixtures of all AAs except the limiting one), no AA antagonisms occurred. One is led to conclude from this work that a deficiency of one AA does not produce the same results as an equal deficiency of another AA, primarily because each individual deficiency involves a unique AA profile over and above the deficiency. And some AA mixtures over and above individual deficiencies are more noxious than others to voluntary food intake. Cieslak and Benevenga (42–44) arrived at conclusions similar to those of Sugahara et al. (41) in rat studies involving excess AA mixtures added to Lys- or Thr-deficient diets. In fact, they concluded that "all AA deficiencies are not alike."
Studies on chicks (45,46), rats (47), and kittens (48,49) lead us to the conclusion that indispensable AAs are inefficient precursors of dispensable AAs. In felids, some of the problems with using excess indispensable AAs to meet the need for dispensable AAs may reside in the relative toxicity of Met that is present in the indispensable AA mixture (48). It seems likely, however, that this may be primarily a felid phenomenon. In most species but not rats or cats, glutamic acid or diammonium citrate can meet the entire need for nonspecific amino nitrogen (45,50–55). Although less efficient as amino donors than glutamate, other dietary (or metabolic) nitrogenous compounds (e.g., nucleic acids, some purines and pyrimidines, urea) can also provide nitrogen for biosynthesis of dispensable AAs (45,54,55).
Efficiency of AA utilization
Considerable difference of opinion exists regarding whether the efficiency of use (for protein accretion) of AAs above maintenance is constant (16–23,56,57) or variable (58–60) in growing animals fed graded levels (from zero to near optimal) of a limiting AA. Other work suggested constant utilization efficiency of a complete AA mixture (16) or of various intact proteins (61,62) when graded levels of each were fed. As pointed out previously, the efficiency above maintenance for retaining ileal digestible AAs is different for different indispensable AAs (18,19–23). Batterham (18) thus estimated efficiency (above maintenance) values of 75, 64, 45, and 38% for retaining (recovering) Lys, Thr, Met, and Trp, respectively, in whole-body protein of growing pigs. Heger et al. (63) also found Trp to have the lowest utilization efficiency among the indispensable AAs. This suggests that even when these AAs are consumed at levels below requirement, true digestible (absorbed) levels of these AAs are retained with surprisingly low rates of efficiency. Why? Is the need for glucose via gluconeogenesis superseding the AA needs for protein synthesis?
Our data on chicks (17,20–23) and pigs (19) together with the data on pigs from Batterham et al. (56), Adeola (57), and Heger et al. (63,64) point to the conclusion that efficiency above maintenance of using individual (limiting) AAs is constant over a wide range of intake levels of the limiting AA. Thus, from zero or near-zero intake to 80–90% of the requirement, efficiency does not decrease with increasing intake but instead remains constant.
Pharmacologic uses of AAs
Although convincing efficacy data are often elusive, pharmacologic uses of AAs are a fertile area of research. Pharmacologic applications of Cys and Arg are used as illustrations here. Both of these AAs have a multitude of functions beyond their roles in protein synthesis.
Cys is used to make specialized (high-Cys) body proteins such as metallothionein and Cys-rich intestinal protein. Also, when Cys is oxidized to cystine, it imparts structural integrity to proteins including enzymes. In its precursor role, Cys functions in glutathione, taurine, and (via sulfate production)3'-phosphoadenosine-5'-phosphosulfate biosynthesis. Cys also functions as a reducing agent. For example, adding L-Cys to a diet containing a toxic level of pentavalent organic As (i.e., the kind of As found as a food contaminant) greatly enhances the toxicity, because it reduces minimally toxic pentavalent organic As to highly toxic trivalent organic As (65). Cys interactions with trace metals are also well known. Thus, when Cys binds to certain trace elements such as Cu, Co, or Se (66,67), reduced gut absorption occurs. Cys and its methylated derivatives (dimercaptopropanol, D-penicillamine) are therefore used clinically to treat the Cu toxicity problems of Wilson's disease (67–71). In contrast, trace elements such as Zn and Fe are absorbed from the gut more efficiently when L-Cys is added to the diet (72–74). Another Cys derivative, N-acetyl-L-Cys, which is fully active as an L-Cys precursor (75,76), is increasingly used for therapeutic applications in clinical situations involving sepsis, respiratory diseases, and various autoimmune deficiency diseases (77,78). It is noteworthy that the above listed pharmacologic effects of oral L-Cys or N-acetyl-L-Cys cannot be duplicated by isomolar levels of L-cystine, L- or DL-Met, or the DL-hydroxy analog of Met, although L-cystine and glutathione do have some antioxidant and mineral chelation activity (66,67).
Animal studies show that Cys is the rate-limiting AA in endogenous protein synthesis (79). Hence, previous work showing increased nitrogen retention when Met alone is given to animals fed a protein-free diet appears due entirely to Met being metabolized to Cys. A plethora of animal growth studies show that the dietary Met requirement is only half as large when surfeit Cys is present in the diet as when Met alone is used to meet the SAA requirement. Are humans different in this regard? Vernon Young has presented arguments that they may be different (80), whereas work from the laboratories of Paul Pencharz and Ron Ball (81) suggest that Cys can indeed spare the Met requirement in humans. It is well to remember that cyst(e)ine (i.e., Cys and cystine) is the most poorly digested AA present in proteins (4,82,83), and heat treatment of proteins reduces cyst(e)ine digestibility even further. Thus, heat processing results in increased disulfide formation, and protein-bound cystine is less digestible than protein-bound Cys (84). Moreover, heat treatment of proteins can also cause some of the Cys to be converted to the cross-linked SAA lanthionine, which has little, if any, SAA bioactivity (85).
Arg is getting increasing attention for a variety of conditions such as endothelial dysfunction, wound healing, trauma, burn injury, small-bowel resection, renal failure, cancer, and diabetes (86–89). The discovery in the late 1980s that Arg is a precursor of nitric oxide and that nitric oxide can be produced in macrophages, endothelial cells, and many other cells (90–93) has led to renewed interest in the biochemistry and nutrition of Arg in both animals and humans. In normal (i.e., healthy) individuals, however, it is hard to envision a scenario where Arg would ever become deficient. The food supply is rich in protein-bound Arg, and in vivo biosynthesis alone is sufficient to meet the protein synthesis and urea cycle needs for Arg in healthy adults (94), similar to the situation in adult gravid and nongravid swine (95,96). Hence, there may be aspects of pharmacologic dosing of Arg in its free AA form that differ from Arg supplied metabolically or consumed as protein-bound Arg.
Final thoughts
Animal studies of AA tolerances are useful, but they also have limitations when extrapolated to humans. Rodents, avians, and pigs consume food in many meals throughout the day, whereas humans are considered "meal eaters." Obviously, taking single AAs without food versus taking them with a large meal could have hugely different consequences. Also, taking a single AA supplement alone is different from taking that same supplement with other AAs or taking it in the form of a peptide or a protein. More work is needed, therefore, on AA versus peptide versus protein sources of AAs in terms of tolerance and safety considerations.
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FOOTNOTES |
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3 Abbreviations used: AA, amino acid; CP, crude protein; SAA, sulfur amino acid; SBM, soybean meal.
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LITERATURE CITED |
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TOPABSTRACTLITERATURE CITED |
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1. Fuller, M. F. (1994) Amino acid requirements for maintenance, body protein accretion and reproduction in pigs. In: Amino Acids in Farm Animal Nutrition (D'Mello, J.P.F., ed.), pp. 155–184. CAB Intl., Wallingford, Oxon, UK.
2. Chung, T. K. & Baker, D. H. (1992) Ideal amino acid pattern for ten kilogram pigs. J. Anim. Sci. 70: 3102–3111.[Abstract]
3. Baker, D. H. (1997) Ideal amino acid profiles for swine and poultry and their applications in feed formulation. BioKyowa Tech. Rev. 9: 1–24.
4. National Research Council (1998) Nutrient Requirements of Swine, 10th rev. ed. National Academy Press, Washington, DC.
5. Baker, D. H. (2000) Recent advances in use of the ideal protein concept for swine feed formulation. Asian-Aus. J. Anim. Sci. 13: 294–301.
6. Baker, D. H. & Han, Y. (1994) Ideal amino acid profile for broiler chicks during the first three weeks posthatching. Poult. Sci. 73: 1441–1447.[Medline]
7. Emmert, J. L. & Baker, D. H. (1997) Use of the ideal protein concept for precision formulation of amino acid levels in broiler diets. J. Appl. Poultry Res. 6: 462–470.
8. Mack, S., Bercovici, D., DeGroote, G., Leclercq, B., Lippens, M., Pack, M., Schutte, J. B. & VanCauwenberghe, S. (1999) Ideal amino acid profile and dietary lysine specification for broiler chicks of 20 to 40 days of age. Br. Poult. Sci. 40: 257–265.[Medline]
9. Baker, D. H., Batal, A. B., Parr, T. M., Augspurger, N. R. & Parsons, C. M. (2002) Ideal ratio (relative to lysine) of tryptophan, threonine, isoleucine and valine for chicks during the second and third week of life. Poult. Sci. 81: 485–494.
10. Baker, D. H., Becker, D. E., Norton, H. W., Jensen, A. H. & Harmon, B. G. (1966) Some qualitative amino acid needs of adult swine for maintenance. J. Nutr. 88: 382–390.
11. Baker, D. H., Becker, D. E., Norton, H. W., Jensen, A. H. & Harmon, B. G. (1966) Quantitative evaluation of the threonine, isoleucine, valine and phenylalanine needs of adult swine for maintenance. J. Nutr. 88: 391–396.
12. Baker, D. H., Becker, D. E., Norton, H. W., Jensen, A. H. & Harmon, B. G. (1966) Quantitative evaluation of the tryptophan, methionine and lysine needs of adult swine for maintenance. J. Nutr. 89: 441–447.
13. Baker, D. H. & Allee, G. L. (1970) Effect of dietary carbohydrate on assessment of the leucine need for maintenance of adult swine. J. Nutr. 100: 277–280.
14. Izquierdo, O. A., Parsons, C. M. & Baker, D. H. (1988) Bioavailability of lysine in L-lysine•HCl. J. Anim. Sci. 66: 2590–2597.
15. Chung, T. K. & Baker, D. H. (1992) Apparent and true digestibility of a crystalline amino acid mixture and of casein: comparison of values obtained with ileal-cannulated pigs and cecectomized cockerels. J. Anim. Sci. 70: 3781–3790.[Abstract]
16. Velu, J. G., Baker, D. H. & Scott, H. M. (1971) Protein and energy utilization by chicks fed graded levels of a balanced mixture of crystalline amino acids. J. Nutr. 101: 1249–1256.
17. Velu, J. G., Scott, H. M. & Baker, D. H. (1972) Body composition and nutrient utilization of chicks fed amino acid diets containing graded amounts of either isoleucine or lysine. J. Nutr. 102: 741–748.
18. Batterham, E. S. (1994) Ileal digestibility of amino acids in feedstuffs for pigs. In: Amino Acids in Farm Animal Nutrition (D'Mello, J.P.F., ed.), pp. 113–131. CAB Intl., Wallingford, Oxon, UK.
19. Chung, T. K. & Baker, D. H. (1992) Efficiency of dietary methionine utilization by young pigs. J. Nutr. 122: 1862–1869.
20. Baker, D. H., Fernandez, S. R., Parsons, C. M., Edwards, H. M., III, Emmert, J. L. & Webel, D. M. (1996) Maintenance requirement for valine and efficiency of its use above maintenance for accretion of whole-body valine and protein in young chicks. J. Nutr. 126: 1844–1851.
21. Edwards, H. M., III, Baker, D. H., Fernandez, S. R. & Parsons, C. M. (1997) Maintenance threonine requirement and efficiency of its use for accretion of whole-body threonine and protein in young chicks. Br. J. Nutr. 78: 111–119.[Medline]
22. Edwards, H. M., III, Fernandez, S. R. & Baker, D. H. (1999) Maintenance lysine requirement and efficiency of using lysine for accretion of whole-body lysine and protein in young chicks. Poult. Sci. 78: 1412–1417.
23. Edwards, H. M., III & Baker, D. H. (1999) Maintenance sulfur amino acid requirements of young chicks and efficiency of their use for accretion of whole-body sulfur amino acids and protein. Poult. Sci. 78: 1418–1423.
24. Edmonds, M. S. & Baker, D. H. (1987) Amino acid excesses for young pigs: effects of excess methionine, tryptophan, threonine or leucine. J. Anim. Sci. 64: 1664–1671.
25. Edmonds, M. S. & Baker, D. H. (1987) Failure of excess dietary lysine to antagonize arginine in young pigs. J. Nutr. 117: 1396–1401.
26. Edmonds, M. S., Gonyou, H. W. & Baker, D. H. (1987) Effect of excess levels of methionine, tryptophan, arginine, lysine or threonine on growth and dietary choice in the pig. J. Anim. Sci. 65: 179–185.
27. Han, Y. & Baker, D. H. (1993) Effects of excess methionine or lysine for broilers fed a corn-soybean meal diet. Poult. Sci. 72: 1070–1074.[Medline]
28. Edmonds, M. S. & Baker, D. H. (1987) 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. 65: 699–705.
29. Koelkebeck, K. W., Baker, D. H., Han, Y. & Parsons, C. M. (1991) Effect of excess lysine, methionine, threonine or tryptophan on production performance of laying hens. Poult. Sci. 70: 1651–1653.[Medline]
30. Allen, N. K., Baker, D. H., Scott, H. M. & Norton, H. W. (1972) Quantitative effect of excess lysine on the ability of arginine to promote chick weight gain. J. Nutr. 102: 171–180.
31. Austic, R. E. & Scott, R. L. (1975) Involvement of food intake in the lysine-arginine antagonism in chicks. J. Nutr. 105: 1122–1131.
32. Czarnecki, G. L., Hirakawa, D. A. & Baker, D. H. (1985) Antagonism of arginine by excess dietary lysine in the growing dog. J. Nutr. 115: 743–752.
33. Hargrove, D. M., Rogers, Q. R., Calvert, C. C. & Morris, J. G. (1988) Effects of dietary excesses of the branched-chain amino acids on growth, food intake and plasma amino acid concentrations of kittens. J. Nutr. 118: 311–320.
34. D'Mello, J.P.F. & Lewis, D. (1970) Amino acid interactions in chick nutrition. 2. The interrelationship between leucine, isoleucine, and valine. Br. Poult. Sci. 11: 313–323.[Medline]
35. Allen, N. K. & Baker, D. H. (1972) Quantitative efficacy of dietary isoleucine and valine for chick growth as influenced by variable quantities of excess dietary leucine. Poult. Sci. 51: 1292–1298.[Medline]
36. Smith, T. K. & Austic, R. E. (1978) The branched-chain amino acid antagonism in chicks. J. Nutr. 108: 1180–1191.
37. Calvert, C. C., Klasing, K. C. & Austic, R. E. (1982) Involvement of food intake and amino acid catabolism in the branched-chain amino acid antagonism in chicks. J. Nutr. 112: 627–635.
38. Tannous, R. I., Rogers, Q. R. & Harper, A. E. (1966) Effect of leucine-isoleucine antagonism on the amino acid pattern of plasma and tissues of the rat. Arch. Biochem. Biophys. 113: 356–361.[Medline]
39. Harper, A. E., Miller, R. H. & Block, K. P. (1984) Branched-chain amino acid metabolism. Annu. Rev. Nutr. 4: 409–454.[Medline]
40. Oestemer, G. A., Hanson, L. E. & Meade, R. J. (1973) Leucine-isoleucine interrelationship in the young pig. J. Anim. Sci. 36: 674–678.
41. Sugahara, M., Baker, D. H. & Scott, H. M. (1969) Effect of different patterns of excess amino acids on performance of chicks fed amino acid deficient diets. J. Nutr. 97: 29–32.
42. Cieslak, D. G. & Benevenga, N. J. (1984) The effect of amino acid excess on utilization by the rat of the limiting amino acid—lysine. J. Nutr. 114: 1863–1870.
43. Cieslak, D. G. & Benevenga, N. J. (1984) The effect of amino acid excess on utilization by the rat of the limiting amino acid—threonine. J. Nutr. 114: 1871–1877.
44. Cieslak, D. G. & Benevenga, N. J. (1984) The effect of amino acid excess on utilization by the rat of the limiting amino acid—lysine and threonine at equalized food intakes. J. Nutr. 114: 1878–1883.
45. Allen, N. K. & Baker, D. H. (1974) Quantitative evaluation of nonspecific nitrogen sources for the growing chick. Poult. Sci. 53: 258–264.[Medline]
46. Stucki, W. P. & Harper, A. E. (1961) Importance of dispensable amino acids for normal growth of chicks. J. Nutr. 74: 377–383.
47. Stucki, W. P. & Harper, A. E. (1962) Effects of altering the ratio of indispensable to dispensable amino acids in diets for rats. J. Nutr. 78: 115–119.
48. Taylor, T. P., Morris, J. G., Willits, N. H. & Rogers, Q. R. (1996) Optimizing the pattern of essential amino acids as the sole source of dietary nitrogen supports near maximal growth in kittens. J. Nutr. 126: 2243–2252.
49. Rogers, Q. R., Taylor, T. P. & Morris, J. G. (1998) Optimizing dietary amino acid patterns at various levels of crude protein for cats. J. Nutr. 128 (suppl.): 2577S–2580S.
50. Hirakawa, D. A. & Baker, D. H. (1988) Comparative performance as well as nitrogen and energy metabolism of young puppies fed three distinctly different experimental dog foods and one commercial product. Companion Anim. Pract. 2: 25–32.
51. Hirakawa, D. A., Olson, L. A. & Baker, D. H. (1984) Comparative utilization of a crystalline amino acid diet and a methionine-fortified casein diet by young rats and mice. Nutr. Res. 4: 891–895.
52. Robbins, K. R. & Baker, D. H. (1978) Development of a semi-synthetic research diet for young swine. Can. J. Anim. Sci. 58: 533–535.
53. Scott, H. M., Dean, W. F. & Smith, R. E. (1963) Studies on the nonspecific nitrogen requirement of chicks fed a crystalline amino acid diet. Poult. Sci. 42: 1305–1306.
54. Baker, D. H. & Molitoris, B. A. (1974) Utilization of nitrogen from selected purines and pyrimidines and from urea by the young chick. J. Nutr. 104: 553–557.
55. Rose, W. C., Smith, L. C., Womack, M. & Shane, M. (1949) The utilization of the nitrogen of ammonium salts, urea, and certain other compounds in the synthesis of nonessential amino acids in vivo. J. Biol. Chem. 181: 307–316.
56. Batterham, E. S., Andersen, L. M., Baigent, D. R. & White, E. (1990) Utilization of ileal digestible amino acids by growing pigs: effects of dietary lysine concentration on efficiency of lysine retention. Br. J. Nutr. 64: 81–94.[Medline]
57. Adeola, L. (1995) Dietary lysine and threonine utilization by young pigs: efficiency for carcass growth. Can. J. Anim. Sci. 75: 445–452.
58. Miller, D. S. & Payne, P. R. (1961) Problems in the prediction of protein values of diets. The influence of protein concentration. Br. J. Nutr. 15: 11–19.[Medline]
59. Heger, J. & Frydrych, Z. (1985) Efficiency of utilization of essential amino acids in growing rats at different levels of intake. Br. J. Nutr. 54: 499–508.[Medline]
60. Gahl, M., Finke, M. D., Crenshaw, T. D. & Benevenga, N. J. (1991) Use of a four-parameter logistic equation to evaluate the response of growing rats to ten levels of each indispensable amino acid. J. Nutr. 121: 1720–1729.
61. Hegsted, D. M. & Neff, R. (1970) Efficiency of protein utilization in young rats at various levels of intake. J. Nutr. 100: 1173–1180.
62. Emmert, J. L., Edwards, H. M., III & Baker, D. H. (2000) Protein and body weight accretion of chicks fed widely varying levels of soybean meal supplemented or unsupplemented with its limiting amino acids. Br. Poult. Sci. 41: 204–213.[Medline]
63. Heger, J., Van Phung, T. & Krizova, L. (2002) 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. 86: 153–165.[Medline]
64. Heger, J., Van Phung, T., Krizova, L., Sustala, M. & Simecek, K. (2003) Efficiency of amino acid utilization in the growing pig at suboptimal levels of intake: branched-chain amino acids, histidine and phenylalanine + tyrosine. J. Anim. Physiol. Anim. Nutr. 87: 52–65.[Medline]
65. Czarnecki, G. L., Baker, D. H. & Garst, J. E. (1984) Arsenic-sulfur amino acid interactions in the chick. J. Anim. Sci. 59: 1573–1581.
66. Robbins, K. R. & Baker, D. H. (1980) Effect of sulfur amino acid level and source on the performance of chicks fed high levels of copper. Poult. Sci. 59: 1246–1253.
67. Baker, D. H. & Czarnecki-Maulden, G. L. (1987) Pharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities. J. Nutr. 117: 1003–1010.
68. Walske, J. M. (1956) Penicillamine: a new oral therapy for Wilson's disease. Am. J. Med. 21: 487–495.[Medline]
69. Smithgall, J. M. (1985) The copper controlled diet: current aspects of dietary copper restriction in management of copper metabolism disorders. J. Am. Diet. Assoc. 85: 609–611.[Medline]
70. Aoyagi, S. & Baker, D. H. (1994) Copper-amino acid complexes are partially protected against inhibitory effects of L-cysteine and L-ascorbate. J. Nutr. 124: 388–395.
71. Persia, M. E., Parsons, C. M. & Baker, D. H. (2004) Amelioration of oral copper toxicity in chicks by dietary additions of ascorbic acid, cysteine and zinc. Nutr. Res. 23: 1709–1718.
72. Snedeker, S. M. & Greger, J. L. (1983) Metabolism of zinc, copper and iron as affected by dietary protein, cysteine and histidine. J. Nutr. 113: 644–652.
73. Layrisse, M., Martinez-Torres, C., Leets, I., Taylor, P. & Ramirez, J. (1984) Effect of histidine, cysteine, glutathione or beef on iron absorption in humans. J. Nutr. 114: 217–223.
74. Hortin, A. E., Bechtel, P. J. & Baker, D. H. (1991) Efficacy of pork loin as a source of zinc, and effect of added cysteine on zinc bioavailability. J. Food Sci. 56: 1505–1508.
75. Baker, D. H. & Han, Y. (1993) Bioavailable level (and source) of cysteine determines protein quality of a commercial enteral product: adequacy of tryptophan but deficiency of cysteine for rats fed an enteral product prepared fresh or stored beyond shelf life. J. Nutr. 123: 541–546.
76. Baker, D. H. (1994) Utilization of precursors for L-amino acids. In: Amino Acids in Farm Animal Nutrition (D'Mello, J.P.F., ed.), pp. 37–64. CAB Intl., Wallingford, Oxon, UK.
77. Baker, D. H. & Wood, R. J. (1992) Cellular antioxidant status and human immunodeficiency virus replication. Nutr. Rev. 50: 15–18.[Medline]
78. Kelly, G. S. (1998) Clinical applications of N-acetylcysteine. Altern. Med. Rev. 3: 114–127.[Medline]
79. Webel, D. M. & Baker, D. H. (1999) Cysteine is the first-limiting amino acid for the utilization of endogenous amino acids in chicks fed a protein-free diet. Nutr. Res. 19: 569–577.
80. Young, V. R. (2001) Got some amino acids to spare? Am. J. Clin. Nutr. 74: 709–711.
81. DiBuono, M., Wykes, L. J., Cole, D.E.C., Ball, R. O. & Pencharz, P. B. (2003) Regulation of sulfur amino acid metabolism in men in response to changes in sulfur amino acid intakes. J. Nutr. 133: 733–739.
82. National Research Council (1994) Nutrient Requirements of Poultry, 9th rev. ed. National Academy Press, Washington, DC.
83. Parsons, C. M., Hashimoto, K., Wedekind, K. J., Han, Y. & Baker, D. H. (1992) Effect of overprocessing on availability of amino acids and energy in soybean meal. Poult. Sci. 71: 133–140.
84. Miller, E. L., Huang, Y. X., Kasinathan, S., Rayner, B., Luzzana, U., Moretti, V. M., Valfr, F., Torrissen, K. R., Jensen, H. B. & Opstvedt, J. (2001) Heat-damaged protein has reduced ileal true digestibility of cysteine and aspartic acid in chicks. J. Anim. Sci. 79 (suppl. 1): 65 (abs.).
85. Robbins, K. R., Baker, D. H. & Finley, J. W. (1980) Studies on the utilization of lysinoalanine and lanthionine. J. Nutr. 110: 907–915.
86. Flynn, N. E., Meininger, C. J., Haynes, T. E. & Wu, G. (2002) The metabolic basis of arginine nutrition and pharmacotherapy. Biomed. Pharmacother. 56: 427–438.[Medline]
87. Wu, G. & Morris, S. M. (1998) Arginine metabolism: nitric oxide and beyond. Biochem. J. 336: 1–17.
88. Wu, G. & Meininger, C. J. (2002) Arginine nutrition and cardiovascular function. J. Nutr. 130: 2626–2629.
89. Meininger, C. J., Marinos, R. S., Hatakeyama, K., Martinez-Zaquilan, R., Rojas, J. D., Kelly, K. A. & Wu, G. (2000) Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. Biochem. J. 349: 353–356.[Medline]
90. Hibbs, J. B., Jr., Taintor, R. R. & Vavrin, Z. (1987) Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235: 473–476.
91. Hibbs, J. B., Jr., Taintor, R. R., Vavrin, Z. & Rachlin, E. M. (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem. Biophys. Res. Commun. 157: 87–94.[Medline]
92. Marletta, M. A., Yoon, P. S., Iyengar, R., Leaf, C. D. & Wishnok, J. S. (1988) Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 27: 8706–8711.[Medline]
93. Palmer, R.M.J., Ashton, D. & Moncada, S. (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333: 664–666.[Medline]
94. Carey, C. P., Kime, Z., Rogers, Q. R., Morris, J. G., Hargrove, D., Buffington, C. A. & Brusilow, S. W. (1987) An arginine-deficient diet in humans does not evoke hyperammonemia or orotic aciduria. J. Nutr. 117: 1734–1739.
95. Easter, R. A., Katz, R. S. & Baker, D. H. (1974) Arginine: a dispensable amino acid for postpubertal growth and pregnancy of swine. J. Anim. Sci. 39: 1123–1128.
96. Easter, R. A. & Baker, D. H. (1976) Nitrogen metabolism and reproductive response of gravid swine fed an arginine-free diet during the last 84 days of gestation. J. Nutr. 106: 636–641.
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