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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: • methionine • cysteine • cystine • homocysteine • N-acetyl-L-cysteine
Sulfur amino acid (SAA)3 nutrition and metabolism have been studied extensively, from both a basic and applied standpoint. Methionine (Met) is the first limiting amino acid (AA) in virtually all poultry diets, primarily because avian diets around the world are based on soybean meal, a protein source that is deficient in SAA. Methionine, however, is also of great interest metabolically because of its role in transmethylation and its transsulfuration to cysteine (Cys). Cysteine, too, is of great interest because of its role in protein synthesis, protein structure, and as a precursor of glutathione (GSH), taurine, coenzyme A, and active sulfate (for 3'-phosphoadenosine-5'-phosphosulfate, i.e., PAPS) biosynthesis.
The review that follows emphasizes SAA animal studies and focuses on 1) transsulfuration efficiency and cyst(e)ine (Cys + cystine) sparing of the Met requirement, 2) Met and Cys precursors, and 3) relative toxicity of SAA. A comprehensive review of SAA metabolism has been published recently (1).
Transsulfuration and the Cys-sparing effect
Transsulfuration involves transfer of the sulfur from Met to serine, resulting in Cys biosynthesis (2–6). On a molar basis, Met is 100% efficient as a precursor of Cys (7,8). The reaction between Cys and cystine is freely reversible such that both compounds are equal in furnishing Cys bioactivity for support of protein synthesis. In young, rapidly growing animals, cyst(e)ine can furnish 50% of the requirement (wt:wt) for SAA (7–14). For older animals (i.e., adult maintenance), cyst(e)ine can furnish >50% of the SAA requirement (15–18).
Young et al. had questioned whether Cys can spare Met in adult humans (19,20). Data from Di Buono et al. (21,22), however, showed that the Met requirement of adult men was roughly one-half as high when determined in the presence of excess dietary Cys as when determined with Met alone (i.e., no dietary Cys). Their results suggested that excess dietary Cys lowers the dietary Met requirement by increasing the remethylation of homocysteine (Hcy) to Met and decreasing the flux of Hcy transsulfuration to Cys. Dietary SAA requirements of humans are expressed as mg·kg–1·d–1. Therefore, the molecular weight difference between Met (149.2 mg/mmol) and Cys (121.2 mg/mmol) comes into play. Thus, even though transsulfuration conversion of Met sulfur to Cys sulfur is 100% efficient (7,8,11,13,23), 149.2 mg of Met (1 mmol) yields only 121.2 mg (1 mmol) of Cys. This, then, should result in a lower total SAA requirement when a proper ratio of Met and Cys is consumed than when Met alone is used to meet the SAA requirement.
As illustrated by the work of Graber and Baker (7,24), 3 separate bioassays (requirement studies) are necessary to clarify the issue of Met sparing by Cys, and purified amino acid diets are required for all 3 bioassays (Table 1). Requirements were based on quantities of SAA needed to achieve maximal body weight gain and food utilization. In several instances where SAA requirement studies have been done, only Assays 1 and 2 have been completed, and these 2 assays lead to an erroneous estimate of Cys sparing. Hence, the results of Assays 2 and 3 make it clear that Cys can furnish 50% (wt:wt) of the dietary requirement for SAA, whereas Assays 1 and 2 suggest that Cys can furnish 55% (700 – 314 ÷ 700) of the total requirement for SAA.
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A fourth bioassay may be helpful if questions persist about the efficiency with which Met furnishes Cys via transsulfuration. This (slope-ratio) assay uses the Met requirement (314 mg·kg–1·d–1) established in Assay 2 (Table 1) wherein the assay diet contained excess Cys. The basal diet for this assay would therefore provide no Cys but enough Met to furnish a Met intake of 314 mg·kg–1·d–1. Then, dietary levels of Met or Cys would be supplemented to provide 0, 125, or 250 mg·kg–1·d–1 of L-Met or L-Cys (i.e., 3 levels of each SAA below the requirement). If done carefully, slope (weight gain in grams vs. intake in milligrams) of the Met response curve should be about 81% that of the Cys response curve in a common-intercept multiple linear regression model (7,8,23). If an assay such as this is done using indirect (e.g., phenylalanine) oxidation methodology in either animals or humans, one would expect slope of the Cys response curve to be more steeply negative than that of the Met response curve.
SAA precursors
Met and Cys isomers. The D-isomer of Met is utilized well as an L-Met precursor, except in apes and humans (14,30–39). Indeed, although the efficacy of D-Met for growth of pigs and dogs is 100% (35,38), the efficacy of D-Met for supporting nitrogen balance of adult humans is only about 30% (30,31).
In species obtaining good efficacy from D-Met, the keto analog must obviously be formed, and this must be subsequently transaminated to L-Met. Although keto-Met is not formed in the (major) transsulfuration pathway of Met degradation, an alternative pathway exists wherein keto-Met is formed (40,41), that is, under conditions of high Met intakes. The keto analog of Met is also an intermediate in the conversion of the DL-OH analog of Met to L-Met. Thus, the keto analog of Met has been shown to have good L-Met efficacy in the chick (42). The keto analog of Cys is not produced in metabolism, so neither the keto analog (43) nor D-Cys (44) has L-Cys bioactivity.
Hydroxy analog of Met.
The 
-hydroxy analog of DL-Met (OH-Met) is an important commercial product. The compound is made chemically, and therefore, it is a 1:1 mixture of D- and L-OH-Met (45). Considerable controversy (46,47) has surrounded the bioactivity of OH-Met, which is available commercially as the calcium salt (86% of the sulfur in Met) or the free acid (88% of the sulfur in Met). It is now well established that 2 separate enzymes are necessary to convert OH-Met to the -keto analog of Met, a dehydrogenase for D-OH-Met and an oxidase for L-OH-Met (48). The keto analog of Met is then transaminated to Met, with branched-chain AA being principal amino donors in avians, but glutamine being the main amino donor in rats (49). Baker and Boebel (45) in chicks and Friedman and Gumbmann (36,50) in mice showed with purified diets that D-OH-Met is more active than L-OH-Met in stimulating growth of animals fed SAA-deficient diets.
Does OH-Met free acid have 88% L-Met bioactivity (weight or concentration basis)? This is what one would expect if OH-Met yielded L-Met with 100% molar efficiency. In avians, Potter (46) estimated, based on an extensive literature review, that OH-Met has 75% of the molar activity of L-Met. This translates to 66% efficacy on a weight or concentration basis (88% x 0.75 = 66%). Table 2 shows OH-Met as having 80% molar efficacy in chicks (14,51). The L-Met-sparing value of OH-Met in pigs is equivocal, with published molar values ranging from 75% (52) to 100% (38,53). DL-OH-Met also is used clinically for renal patients (54), but its efficacy relative to L-Met is not known (55).
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-glutamylcysteinylglycine, i.e., GSH), taurine, lanthionine, S-methyl-L-Met (SMM), and dimethylsulfoniopropionate are found in food and feed ingredients consumed by animals and humans (56–61). Taurine and GSH are constituents of animal-based products, but GSH is also present in some plant-based food products. Lanthionine is a cross-linked SAA that is formed in food products that have been exposed to heat. It is prominent in feather meal and poultry by-product meals used in animal feeds. Only plant-based foods contain SMM. Taurine has no SAA-sparing activity in either chicks (8) or rats (62), although it may be limiting in diets for neonatal infants (63). Glutathione is fully effective on a molar basis in furnishing L-Cys (42,64,65). Lanthionine in foods can exist in 8 different isomeric forms (66–68). That absorbed from the gut can be cleaved by cystathionase (69), releasing either D- or L-Cys. Robbins et al. (70) conducted a quantitative study in chicks that suggested that DL-lanthionine has 35% L-Cys bioactivity.
S-Methylmethionine (SMM) is an analog of S-adenosylmethionine (SAM), with a methyl group substituted for the adenosyl group. This compound is unique to plants and is found in measurable-to-high concentration in corn, cabbage, tomatoes, celery, spinach, garlic, and in soy flours and meals (60,61,71–73). Several rodent studies have suggested that SMM has Met-sparing activity (74–77), but recent chick work (61) has shown that L-SMM will spare Met only under conditions where diets are limiting in choline and betaine. With diets adequate in Met but deficient in choline, SMM has been suggeted as being capable of directly methylating phosphatidylethanolamine to form phosphatidylcholine and then choline (61).
SAA oxidation products. Methionine and cyst(e)ine in foods are subject to oxidative losses wherein Met is converted to either Met sulfoxide or Met sulfone, and Cys is oxidized to cysteic acid. These compounds are often found in milk-based foods because hydrogen peroxide is frequently used for sterilization purposes (78–80). Neither L-Met sulfone nor L-cysteic acid has SAA bioactivity when fed to rats (81), but L-Met sulfoxide has 60% and 85% bioactivity for rats and mice, respectively (14).
Homocyst(e)ine. Considerable research has been carried out with Hcy, an intermediate in the transsulfuration pathway (82). This AA is not a constituent of body proteins, but it accumulates in tissues and body fluids of patients afflicted with homocystinemia and homocystinuria (83). Homocysteine has also been implicated as a causative factor in vascular disease. In virtually all cases where Hcy or its oxidation product (homocystine) has been used in nutrition research, the racemic DL mixture has been used, yet the efficacy of the separate isomers was not known. Potentially, Hcy (or homocystine) could serve as a precursor for either Cys or Met. Work with chicks and rats from our laboratory established that D- and L-Hcy have considerably different bioactivities when serving as an oral source of Met or Cys (84,85). As might be expected, both isomers of Hcy are more effective precursors of L-Cys than of L-Met. With diets adequate in Cys and deficient in Met, L-Hcy had 65% of the growth-promoting activity of L-Met, whereas D-Hcy was only 7% as effective as L-Met (14).
Palatable SAA precursors for food supplementation.
Although supplementation of animal diets with either DL-Met or DL-OH-Met has become common, adding bioavailable SAA activity to diets for humans has been held back because 1) Met and OH-Met are unpalatable to humans, 2) L-Cys is too toxic for routine use, and 3) L-cystine is relatively insoluble, making it inappropriate for liquefied diets (i.e., enteral and parenteral applications). Although GSH (Cys precursor) is soluble as well as palatable, it is expensive and also unstable. Thus, there is great interest in finding palatable and soluble precursors of Met or Cys for human applications. Acetylation of the -amino group of either L-Met or L-Cys results in compounds that are palatable (86,87) and have full SAA bioactivity (88–91), although N-acetyl-D-Met has no Met-sparing activity (35,88,89). An added virtue of N-acetyl-L-Met is that it is an effective precursor of both Met and Cys, whereas N-acetyl-L-Cys can provide only Cys bioactivity. Moreover, acetylation of the -amino group of Met or Cys protects these SAA against Maillard destruction (92). Clinical interest in both N-acetyl-L-Cys and lipoic acid (causes increased intracellular cysteine and GSH) has increased in recent years. Thus, the antioxidant activity of these compounds has been of interest in treating chronic bronchitis, acetominophen hepatotoxicity, diabetes, cancer, sepsis, HIV infection, heart disease, and acute myocardial infarction (93–96).
Williamson and Meister (97) identified a new Cys precursor, L-2-oxothiazolidine-4-carboxylic acid (OTC), and this compound can serve as an oral precursor of L-Cys (or GSH). Subsequent work indicated that OTC has 80% and 70% L-Cys bioactivity in chicks and rats, respectively (98). Other L-Cys precursors have also been shown to be effective precursors of L-Cys, although quantitative efficacy values are not available. Thus, for improving glycemic control in diabetic mice, orally administered N-acetyl-L-Cys, S-allyl-L-Cys, S-ethyl-L-Cys, S-methyl-L-Cys, and S-propyl-L-Cys were all found to be efficacious (96).
SAA toxicity
Because excess ingestion of Met causes a greater growth depression than that caused by other AA (99–102), the literature is extensive on Met imbalance and toxicity (103,104). Less is known about cyst(e)ine toxicity, but both Cys and its oxidation product cystine are well established as being relatively toxic at high levels of intake (103,104). It is not my intent to repeat the information contained in these excellent and comprehensive reviews. Instead, a brief summary will be given of newer information on SAA toxicity.
It is clear that the growth depressions and biochemical lesions caused by excess Met consumption are different from those caused by excess Cys or cystine consumption. Indeed, although considerable work has been done on metabolites of Met (e.g., Hcy and cystathionine) and Cys (e.g., taurine, cysteic acid, sulfate), it appears that excess Met and cyst(e)ine per se are primarily causative. Supplemental glycine is definitely ameliorative of Met toxicity, but whether this is because of its role in detoxifying the methyl group of Met (i.e., for synthesis of either sarcosine or creatine) or for its role as a precursor of serine (i.e., for synthesis of cystathionine from Hcy) is not clear. However, supplemental glycine and to a lesser extent serine definitely enhance methionine oxidation (105). Nothing as yet has been shown to ameliorate cyst(e)ine toxicity, at least nothing in the way of an AA supplement.
Most of the work that has been done with excess dietary levels of cyst(e)ine has used cystine rather than Cys. And even though the oxidized form (cystine) and reduced form (Cys) of these SAA are equal for promoting growth of animals fed diets deficient in cyst(e)ine and adequate in Met (7,23), they produce very different results when administered in the pharmacologic dosing range (106). Cysteine is absorbed from the gut faster than cystine (107) and is a strong reducing agent (108). Moreover, it has the ability to chelate trace minerals in the gut and in the body (106), and with its free sulfhydryl group it can readily bind plasma proteins (109). Harper et al. (103) observed 50% mortality in rats fed a casein diet (10 g/100 g) supplemented with 2.4 g/100 g L-Cys free base.
We recently studied graded levels of supplemental SAA (0, 1, 2, 3, or 4 g/100 g) added to a standard corn–soybean meal diet (23 g/100 g protein) for young chicks (R. N. Dilger and D. H. Baker, University of Illinois, unpublished data). Thus, 0, 1, 2, 3, or 4 g/100 g of L-Met, L-Cys, or L-cystine as well as levels of N-acetyl-L-Cys equimolar to the L-Cys addition were supplemented. Because the basal diet contained Met and cyst(e)ine at their required concentrations for maximal chick growth (i.e., 0.50 g/100 g of each), the supplemental SAA concentrations represented 0, 3, 5, 7, and 9 times the required level of either Met or Cys. The 1 g/100 g additions, regardless of SAA source, had no effect on growth rate. Likewise, 2 g/100 g of supplemental cystine or N-acetyl-L-Cys were without effect on chick growth. This same level of supplemental Met, however, depressed weight gain by 34%, and 2 g/100 g of added L-Cys reduced weight gain by 10%. At 3 g/100 g of L-Cys, half of the chicks died by day 5 of the 9-d bioassay; and 92% mortality occurred by day 5 when 4 g/100 g of L-Cys was supplemented. No mortality occurred at any level of supplemental Met, cystine, or N-acetyl-Cys, although the growth depression at 4 g/100 g of Met was severe (94%). With 4 g/100 g of supplemental L-cystine or an isosulfurous level of N-acetyl-L-Cys, growth depressions were 20% and 34%, respectively. That excess dietary L-cystine and N-acetyl-L-Cys were far less noxious than L-Cys suggests these SAA compounds may have been absorbed from the gut more slowly than Cys, and with N-acetyl-L-Cys, it may have been deacetylated more slowly such that tissue concentrations of Cys could not reach the same levels as those caused by Cys itself. How the intestine metabolizes Cys, cystine, and N-acetyl-L-Cys is not clear, but it is well established that as much as half of whole-body Cys oxidation occurs in splanchnic tissues (110–112). Also, the gut is capable of not only substantial Cys oxidation but also GSH synthesis. Clearly, something is different in how the body handles oral L-Cys, L-cystine, and N-acetyl-L-Cys, resulting in a different toxicity profile for each compound. Pharmacokinetic studies with N-acetyl-L-Cys have demonstrated that <10% of orally administered N-acetyl-L-Cys is absorbed into portal blood as N-acetyl-L-Cys per se (113). Thus, first-pass metabolism in the gut wall causes formation of cysteine, GSH, and inorganic sulfate.
Among the most consistent and noteworthy features of Met toxicity is splenic hemosideroses caused by hemolytic anemia (40,41,104,114). Excess dietary Hcy does not cause this biochemical lesion, but supplemental glycine does have some efficacy in lowering iron deposition in the spleen caused by a large excess of Met (114). It appears, therefore, that intermediates in the alternate transaminative pathway of Met degradation (e.g., 3-methylthiopropionate) are responsible for the marked iron deposition in the spleen of animals consuming large excesses of Met. Indeed, graded Met dosing studies have revealed that blood hemoglobin is inversely proportional and spleen iron concentration directly proportional to the weight gain depression caused by excess dietary Met (114).
With excess cyst(e)ine ingestion, brain lesions and retinal degeneration are the most outstanding features (115,116), although with the reduced compound (Cys) most would agree that death is the most pernicious feature. Fortunately, most of the clinical uses for cyst(e)ine (93,94,117–119) have employed N-acetylcysteine, a compound that, based on rat and chick studies, is much safer than Cys itself.
Recapitulation
Both Met and Cys have a multitude of functions in the body apart from their role in protein synthesis. Methionine via SAM is important in methylation reactions, and it also functions to provide Cys via transsulfuration. Cysteine is a precursor for GSH, taurine, PAPS, and coenzyme A, and it plays an important role in protein structure and as an acceptor of Se for synthesis of selenoproteins and enzymes. It is the first limiting AA for endogenous protein synthesis (120), and it is a major AA constituent of specialized proteins such as metallothionein (MT), Cys-rich intestinal protein (CRIP), and gut mucin. In its reduced state, Cys can bind or chelate several trace elements, which likely explains why it is well established as being capable of increasing iron and zinc absorption but decreasing copper absorption and excretion (106,121–125). Cysteine is also a strong reducing agent, and it has even been proposed to be a cytokine (126).
Both Met and Cys are quite toxic at dietary concentrations 5 times or more above required levels. It seems very questionable whether any Met or cyst(e)ine compound should be available as an over-the-counter nonprescription product.
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FOOTNOTES |
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3 Abbreviations used: AA, amino acid; Cys, cysteine; GSH, glutathione; Hcy, homocysteine; Met, methionine; OH-Met, DL-hydroxy analog of Met; PAPS, 3'-phosphoadenosine-5'–phosphosulfate; RBV, relative oral bioavailability; SAA, sulfur amino acid(s); SAM, S-adenosylmethionine; SMM, S-methylmethionine.
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LITERATURE CITED |
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TOPABSTRACTLITERATURE CITED |
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1. Stipanuk MH. Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr. 2004;24:539–77.[Medline]
2. Womack M, Rose WC. The partial replacement of dietary methionine by cystine for purposes of growth. J Biol Chem. 1941;141:375–9.
3. du Vigneaud V, Kilmer GW, Rachele JR, Cohn M. On the mechanism of the conversion in vivo of methionine to cystine. J Biol Chem. 1944;155:645–51.
4. du Vigneaud V. Trail of research in sulfur chemistry and metabolism and related fields. Ithaca: Cornell University Press; 1952.
5. Finkelstein JD, Mudd SH. Transsulfuration in mammals. The methionine-sparing effect of cystine. J Biol Chem. 1967;242:873–80.
6. Finkelstein JD, Martin JJ, Harris BJ. Methionine metabolism in mammals. The methionine-sparing effect of cystine. J Biol Chem. 1988;263:11750–4.
7. Graber G, Baker DH. Sulfur amino acid nutrition of the growing chick: quantitative aspects concerning the efficacy of dietary methionine, cysteine and cystine. J Anim Sci. 1971;33:1005–11.
8. Sasse CE, Baker DH. Sulfur utilization in the chick with emphasis on the effect of inorganic sulfate on the cystine-methionine interrelationship. J Nutr. 1974;104:244–51.
9. Sowers JE, Stockland WL, Meade RJ. L-Methionine and L-cystine requirements of the growing rat. J Anim Sci. 1972;35:782–8.
10. Teeter RG, Baker DH, Corbin JE. Methionine and cystine requirements of the cat. J Nutr. 1978;108:291–5.
11. Halpin KM, Baker DH. Selenium deficiency and transsulfuration in the chick. J Nutr. 1984;114:606–12.
12. Hirakawa DA, Baker DH. Sulfur amino acid nutrition of the growing puppy: determination of dietary requirements for methionine and cystine. Nutr Res. 1985;5:631–42.
13. Chung TK, Baker DH. Maximal portion of the young pig's sulfur amino acid requirement that can be furnished by cystine. J Anim Sci. 1992;70:1182–7.[Abstract]
14. Baker DH. Utilization of precursors for L-amino acids. In: D'Mello JPF, editor. Amino acids in farm animal nutrition. Wallingford, Oxon: CAB International; 1994. p. 37–64.
15. Baker DH, Becker DE, Norton HW, Jensen AH, Harmon BG. Quantitative evaluation of the tryptophan, methionine and lysine needs of adult swine for maintenance. J Nutr. 1966;89:441–7.
16. Said AK, Hegsted DM. Response of adult rats to low dietary levels of essential amino acids. J Nutr. 1970;100:1363–75.
17. Fuller MF, McWilliam R, Wang TC, Giles LR. The optimum dietary amino acid pattern for growing pigs. 2. Requirements for maintenance and for protein accretion. Br J Nutr. 1989;62:255–67.[Medline]
18. Rose WC, Wixom RL. The amino acid requirements of man: XIII. The sparing effect of cystine on the methionine requirement. J Biol Chem. 1955;216:763–74.
19. Fukagawa NK, Yu YM, Young VR. Methionine and cysteine kinetics at different intakes of methionine and cysteine in elderly men and women. Am J Clin Nutr. 1998;68:380–8.[Abstract]
20. Young VR. Got some amino acids to spare? Am J Clin Nutr. 2001;74:709–11.
21. Di Buono M, Wykes LJ, Ball RO, Pencharz PB. Dietary cysteine (CYS) reduces the methionine (MET) requirement in adult males. Am J Clin Nutr. 2001;74:761–6.
22. Di Buono M, Wykes LJ, Cole DEC, Ball RO, Pencharz PB. Regulation of sulfur amino acid metabolism in men in response to changes in sulfur amino acid intakes. J Nutr. 2003;133:733–9.
23. Graber G, Scott HM, Baker DH. Sulfur amino acid nutrition of the growing chick: effect of age on the capacity of cystine to spare dietary methionine. Poult Sci. 1971;50:1450–5.[Medline]
24. Baker DH. Problems and pitfalls in animal experiments designed to establish dietary requirements for essential nutrients. J Nutr. 1986;116:2339–49.
25. Parsons CM, Hashimoto K, Wedekind KJ, Han Y, Baker DH. Effect of overprocessing on availability of amino acids and energy in soybean meal. Poult Sci. 1992;71:133–40.
26. National Research Council. Nutrient requirements of poultry, 9th ed. Washington, DC: National Academy Press, 1994.
27. Miller EL, Huang YX, Kasinathan S, Rayner B, Luzzana U, Moretti VM, et al. Heat-damaged protein has reduced ileal true digestibility of cysteine and aspartic acid in chicks. [abstract] J Anim Sci. 2001;79: Suppl 1:65.
28. Sasse CE, Baker DH. Factors affecting sulfate-sulfur utilization by the young chick. Poult Sci. 1974;53:652–62.[Medline]
29. Smith JT. An optimal level of inorganic sulfate for the diet of a rat. J Nutr. 1973;103:1008–11.
30. Zezulka AY, Calloway DH. Nitrogen retention in men fed isolated soybean protein supplemented with L-methionine, D-methionine, N-acetyl-L-methionine, or inorganic sulfate. J Nutr. 1976;106:1286–91.
31. Kies C, Fox H, Aprahamian S. Comparative value of L-, DL- and D-methionine supplementation of an oat-based diet for humans. J Nutr. 1975;105:809–14.
32. Berg CP. Utilization of the D-amino acids. In: Albanese AA, editor. Protein and amino acid nutrition. New York: Academic Press; 1959. p. 57–66.
33. Stegink LD, Moss J, Printen KJ, Cho ES. D-Methionine utilization in adult monkeys fed diets containing DL-methionine. J Nutr. 1980;110:1240–6.
34. Cho ES, Anderson DW, Filer LJ, Stegink LD. D-Methionine utilization in young miniature pigs, adult rabbits, and adult dogs. J Parenter Enterol Nutr. 1980;4:544–7.
35. Burns RA, Milner JA. Sulfur amino acid requirements of immature beagle dogs. J Nutr. 1981;111:2117–24.
36. Friedman M, Gumbmann MR. Nutritional value and safety of methionine derivatives, isomeric dipeptides and hydroxy analogs in mice. J Nutr. 1988;118:388–97.
37. Funk MA, Hortin AE, Baker DH. Utilization of D-methionine by growing rats. Nutr Res. 1990;10:1029–34.
38. Chung TK, Baker DH. Utilization of methionine isomers and analogs by the pig. Can J Anim Sci. 1992;72:185–8.
39. Sunde ML. Amino acids in avian nutrition. 6. Utilization of D- and DL-amino acids and analogs. Poult Sci. 1972;51:44–55.[Medline]
40. Mitchell AD, Benevenga NJ. The role of transamination in methionine oxidation in the rat. J Nutr. 1978;108:67–78.
41. Steele RD, Benevenga NJ. Identification of 3-methyl-thiopropionic acid as an intermediate in mammalian methionine metabolism in vitro. J Biol Chem. 1978;253:7844–9.
42. Harter JM, Baker DH. Sulfur amino acid activity of glutathione, DL--hydroxy methionine, and -keto methionine in chicks. Proc Soc Exp Biol Med. 1977;156:201–4.[Medline]
43. Meister A, Fraser PE, Tice SV. Enzymatic desulfuration of ß-mercaptopyruvate. J Biol Chem. 1954;206:561–75.
44. Baker DH, Harter JM. D-Cystine utilization by the chick. Poult Sci. 1978;57:562–3.[Medline]
45. Baker DH, Boebel KP. Utilization of D- and L-isomers of methionine and methionine hydroxy analogue as determined by chick bioassay. J Nutr. 1980;110:959–64.
46. Potter LM. Limiting amino acids in poultry diets. Proc Carolina Poult Nutr Conf. 1984;9:33–40.
47. Baker DH. Utilization of isomers and analogs of amino acids and other sulfur-containing compounds. Prog Food Nutr Sci. 1986;10:133–78.[Medline]
48. Dibner JJ, Knight CD. Conversion of 2-hydroxy-4-(methylthio) butanoic acid to L-methionine in the chick: a stereospecific pathway. J Nutr. 1984;114:1716–23.
49. Austic RE, Rangel-Lugo M. Metabolism of methionine sources in the chicken. Procceedings of the Degussa Technical Symposium; 1992; Indianapolis, IN.
50. Friedman M, Gumbmann MR. The utilization and safety of isomeric sulfur-containing amino acids in mice. J Nutr. 1984;114:2301–10.
51. Boebel KP, Baker DH. Efficacy of calcium salt and free acid forms of methionine hydroxy analog for chicks. Poult Sci. 1982;61:1167–75.
52. Kim BG, Lindemann MD, Cromwell GL, Rademacher M. Efficacy of liquid DL-methionine hydroxy analog free acid and DL-methionine as methionine sources for pigs [abstract]. Proc Midwest Am Soc Anim Sci. 2005;36.
53. Gaines AM, Yi GF, Ratliff BW, Srichana P, Kendall DC, Allee GL, Knight CD, Perryman KR. Estimation of the ideal ratio of true ileal digestible sulfur amino acids: lysine in 8- to 26-kg nursery pigs. J Anim Sci. 2005;83:2527–34.
54. Anonymous. Dietary substitution of essential amino acids by their -keto or -hydroxy analogues. Nutr Rev. 1976;34:22–3.[Medline]
55. Baker DH. Utilization of methionine analogues. J Nutr. 1976;106:1376–7.
56. Baker DH, Blitenthal RC, Boebel KP, Czarnecki GL, Southern LL, Willis GM. Protein-amino acid evaluation for steam-processed feather meal. Poult Sci. 1981;60:1865–72.
57. Cho ES, Johnson N, Snider BC. Tissue glutathione as a cyst(e)ine reservoir during cystine depletion in growing rats. J Nutr. 1984;114:1853–62.
58. Wiezbicker GT, Hagen TM, Tones DP. Glutathione in food. J Food Composition Anal. 1989;2:327–37.
59. Glass EN, Czarnecki-Maulden GL. Taurine concentration in different food products. [abstract] FASEB J. 1990;4:799.
60. Hanson AD, Rivoal J, Paquet L, Gage DA. Biosynthesis of 3-dimethylsulfoniopropionate in Wollastonia biflora: evidence that S-methylmethionine is an intermediate. Plant Physiol. 1994;105:103–10.[Abstract]
61. Augspurger NR, Scherer CS, Garrow TA, Baker DH. Dietary S-methylmethionine, a component of foods, has choline-sparing activity in chickens. J Nutr. 2005;135:1712–17.
62. Martin WG, Truex CR, Tarka SM, Hill LJ, Gorby WG. The synthesis of taurine from sulfate. VIII. A constitutive enzyme in mammals. Proc Soc Exp Biol Med. 1974;147:563–65.[Medline]
63. Rigo J, Senterre J. Is taurine essential for neonates? Biol Neonate. 1977;32:73–6.[Medline]
64. Dyer HM, du Vigneaud V. The utilization of glutathione in connection with a cystine-deficient diet. J Biol Chem. 1936;115:543–9.
65. Boebel KP, Baker DH. Blood and liver concentrations of glutathione, and plasma concentrations of sulfur-containing amino acids, in chicks fed deficient, adequate or excess levels of dietary cysteine. Proc Soc Exp Biol Med. 1983;172:498–501.[Abstract]
66. Jones DB, Divine JP, Horn MJ. A study of the availability of mesolanthionine for the promotion of growth when added to a cystine-deficient diet. J Biol Chem. 1942;146:571–5.
67. Jones DB, Caldwell A, Horn MJ. The availability of DL-lanthionine for the promotion of growth in young rats when added to a cystine- and methionine-deficient diet. J Biol Chem. 1948;176:65–9.
68. Snow JT, Finley JW, Friedman M. Relative reactivities of sulfhydryl groups with N-acetyl dehydroalanine and N-acetyl dehydroalanine ester. Int J Pept Protein Res. 1976;8:57–64.[Medline]
69. Cavallini D, DeMarco C, Mondovi B, Mori BG. The cleavage of cystine by cystathionase and the transsulfuration of hypotaurine. Enzymologia. 1960;22:161–73.[Medline]
70. Robbins KR, Baker DH, Finley JW. Studies on the utilization of lysinoalanine and lanthionine. J Nutr. 1980;110:907–15.
71. Grunau JA, Swiader JM. Chromatographic quantitation of free amino acids: S-methylmethionine, methionine and lysine in corn. J Plant Nutr. 1991;14:653–62.
72. Kim GH, Hong E-Y, Kang E-J, Jeong Y, Kim E-S. Vitamin U in medicinal food plants. [abstract] FASEB J. 2003;18:46.
73. Kovatscheva EG, Popova JG. S-Methylmethionine content in plant and animal tissues and stability during storage. Nahrung. 1977;21:465–72.[Medline]
74. Bennett MA. The replaceability of dl-methionine in the diet of the albino rat with dl-methionine sulfone and dl-methionine methylsulfonium chloride. J Biol Chem. 1941;141:573–8.
75. Stekol JA. Synthetic pathways of methionine, cysteine, and threonine. In: McElroy WD, Glass HB, editors. A symposium on amino acid metabolism. Baltimore, Johns Hopkins Press; 1955. p. 509–57.
76. Matsuo T, Seri K, Kato T. Comparative effects of S-methylmethionine (vitamin U) and methionine on choline-deficient fatty liver in rats. Arzneimittelforschung. 1980;30:68–9.[Medline]
77. Hegedus M, Fekete S, Andrasofszky E, Tamas J, Kovari L. Bioavailability of methionine-hydroxyl-analog free acid and S-methyl-methionine in the growing rat. Acta Vet Hung. 1992;40:145–50.[Medline]
78. Fox PF, Kosikowski FV. Some effects of hydrogen peroxide on casein and its implications in cheese making. J Dairy Sci. 1967;50:1183–8.
79. Yang SF. Sulfoxide formation from methionine or its sulfide analogs during aerobic oxidation of sulfite. Biochemistry. 1970;9:5008–14.[Medline]
80. Anderson GH, Li GSK, Jones JO, Bender F. Effect of hydrogen peroxide treatment on the nutritional quality of rapeseed flour fed to weanling rats. J Nutr. 1975;105:317–25.
81. Anderson GH, Ashley DVM, Jones JD. Utilization of L-methionine sulfoxide, L-methionine sulfone and cysteic acid by the weanling rat. J Nutr. 1976;106:1108–14.
82. Dyer HM, du Vigneaud V. A study of the availability of D- and L-homocystine for growth purposes. J Biol Chem. 1935;109:477–80.
83. Mudd SH, Finkelstein JD, Irreverre F, Laster L. Homocystinuria: an enzymatic defect. Science. 1964;143:1443–5.
84. Harter JM, Baker DH. Sulfur amino acid activity of D- and L-homocysteine for chicks. Proc Soc Exp Biol Med. 1978;157:139–43.[Medline]
85. Baker DH, Czarnecki GL. Transmethylation of homocysteine to methionine: efficiency in the rat and chick. J Nutr. 1985;115:1291–9.
86. Balance PE. Production of volatile compounds related to the flavor of foods from the Strecker degradation of DL-methionine. J Sci Food Agric. 1961;12:532–6.
87. Damico R. An investigation of N-substituted methionine derivatives for food supplementation. J Agric Food Chem. 1975;23:30–3.[Medline]
88. Boggs RW, Rotruck JT, Damico RA. Acetylmethionine as a source of methionine for the rat. J Nutr. 1975;105:326–30.
89. Baker DH. Efficacy of the D- and L-isomers of N-acetylmethionine for chicks fed diets containing either crystalline amino acids or intact protein. J Nutr. 1979;109:970–4.
90. Baker DH, Han Y. 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 shelflife. J Nutr. 1993;123:541–6.
91. Shoveller AK, Brunton JA, Brand O, Pencharz PB, Ball RO. N-Acetylcysteine is a highly available precursor for cysteine in the neonatal piglet receiving total parenteral nutrition. J Parenter Enterol Nutr. 2005; in press.
92. Baker DH, Bafundo KW, Boebel KP, Czarnecki GL, Halpin KM. Methionine peptides as potential food supplements: efficacy and susceptibility to Maillard browning. J Nutr. 1984;114:292–7.
93. Atmaca G. Antioxidant effects of sulfur-containing amino acids. Yonsei Med J. 2004;45:776–88.[Medline]
94. Santangelo F. Intracellular thiol concentration modulating inflammatory response: influence on the regulation of cell functions through cysteine prodrug approach. Curr Med Chem. 2003;10:2599–610.[Medline]
95. Quadrilatero J, Hoffman-Goetz L. N-Acetyl-L-cysteine protects intestinal lymphocytes from apoptotic death after acute exercise in adrenalectomized mice. Am J Physiol Regul Integr Comp Physiol. 2005;288:R1664–72.
96. Hsu C, Yen H, Yin M, Tsai C, Hsieh C. Five cysteine-containing compounds delay diabetic deterioration in BALB/cA mice. J Nutr. 2004;134:3245–9.
97. Williamson JM, Meister A. Stimulation of hepatic glutathione formation by administration of L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-prolinase substrate. Proc Natl Acad Sci USA. 1981;78:936–9.
98. Chung TK, Funk MA, Baker DH. L-2-Oxothiazolidine-4-carboxylate as a cysteine precursor: efficacy for growth and hepatic glutathione synthesis in chicks and rats. J Nutr. 1990;120:158–65.
99. Muramatsu K, Odagiri H, Morishita S, Takeuchi H. Effect of excess levels of individual amino acids on growth of rats fed casein diets. J Nutr. 1971;101:1117–26.
100. Edmonds MS, Gonyou HW, Baker DH. Effects 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.
101. Edmonds MS, Baker DH. Amino acid excesses for young pigs: effects of excess methionine, tryptophan, threonine or leucine. J Anim Sci. 1987;64:1664–71.
102. 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.
103. Harper AE, Benevenga NJ, Wohlhueter RM. Effects of ingestion of disproportionate amounts of amino acids. Physiol Rev. 1970;50:428–558.
104. FASEB Life Sciences Research Office. Safety of amino acids used as dietary supplements. Washington, DC: FASEB; 1992.
105. Benevenga NJ, Harper AE. Effect of glycine and serine on methionine metabolism in rats fed diets high in methionine. J Nutr. 1970;100:1205–14.
106. Baker DH, Czarnecki-Maulden GL. Pharmacologic role of cysteine in ameliorating or exacerbating mineral toxicities. J Nutr. 1987;117:1003–10.
107. Silk DB, Perrett D, Stephens AD, Clark ML, Scowen EF. Intestinal absorption of cystine and cysteine in normal human subjects and patients with cystinuria. Clin Sci Mol Med. 1974;47:393–7.[Medline]
108. Czarnecki GL, Baker DH, Garst JE. Arsenic-sulfur amino acid interactions in the chick. J Anim Sci. 1984;59:1573–81.
109. Malloy MH, Rassin DK, Gaull GE. Plasma cyst(e)ine in homocyst(e)inemia. Am J Clin Nutr. 1981;34:2619–21.
110. Stoll B, Henry J, Reeds PJ, Yu H, Jahoor F, Burrin DG. Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets. J Nutr. 1998;128:606–14.
111. Stipanuk MH, Rotter MA. Metabolism of cysteine, cysteinesulfinate and cysteinesulfonate in rats fed adequate and excess levels of sulfur-containing amino acids. J Nutr. 1984;114:1426–37.
112. Shoveller AK, Stoll B, Ball RO, Burrin DG. Nutritional and functional importance of intestinal sulfur amino acid metabolism. J Nutr. 2005;135:1609–12.
113. Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol. 1988;34:77–82.[Medline]
114. Harter JM, Baker DH. Factors affecting methionine toxicity and its alleviation in the chick. J Nutr. 1978;108:1061–70.
115. Pedersen OO, Karlsen RL. The toxic effect of L-cysteine on the rat retina: a morphological and biochemical study. Invest Ophthalmol Vis Sci. 1980;19:886–92.
116. Sturman JA, Messing JM, Gargano AD, Rerecich M, Imaki H, Rudelli R. Cystine neurotoxicity is increased by taurine deficiency. Neurotoxicology. 1989;10:15–28.[Medline]
117. Kalebic T, Kinter A, Poli G, Anderson ME, Meister A, Fauci AS. Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. Proc Natl Acad Sci USA. 1991;88:986–90.
118. Baker DH, Wood RJ. Cellular antioxidant status and human immunodeficiency virus replication. Nutr Rev. 1992;50:15–8.[Medline]
119. Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998;3:114–27.[Medline]
120. Webel DM, Baker DH. Cysteine is the first-limiting amino acid for the utilization of endogenous amino acids in chicks fed a protein-free diet. Nutr Res. 1999;19:569–77.
121. Aoyagi S, Baker DH. Copper-amino acid complexes are partially protected against inhibitory effects of L-cysteine and L-ascorbate. J Nutr. 1994;124:388–95.
122. Persia ME, Parsons CM, Baker DH. Amelioration of oral copper toxicity in chicks by dietary additions of ascorbic acid, cysteine and zinc. Nutr Res. 2004;23:1709–18.
123. Snedeker SM, Greger JL. Metabolism of zinc, copper and iron as affected by dietary protein, cysteine and histidine. J Nutr. 1983;113:644–52.
124. Layrisse M, Martinez-Torres C, Leets I, Taylor P, Ramirez J. Effect of histidine, cysteine, glutathione or beef on iron absorption in humans. J Nutr. 1984;114:217–23.
125. Hortin AE, Bechtel PJ, Baker DH. Efficacy of pork loin as a source of zinc, and effect of added cysteine on zinc bioavailability. J Food Sci. 1991;56:1505–8.
126. Gmünder H, Eck HP, Benninghoff B, Roth S, Droge W. Macrophages regulate intracellular glutathione levels of lymphocytes. Evidence for an immunoregulatory role of cysteine. Cell Immunol. 1990;129:32–46.[Medline]
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