Amino Acids

, Volume 45, Issue 3, pp 463–477 | Cite as

Glycine metabolism in animals and humans: implications for nutrition and health

  • Weiwei Wang
  • Zhenlong WuEmail author
  • Zhaolai Dai
  • Ying Yang
  • Junjun Wang
  • Guoyao WuEmail author
Invited Review


Glycine is a major amino acid in mammals and other animals. It is synthesized from serine, threonine, choline, and hydroxyproline via inter-organ metabolism involving primarily the liver and kidneys. Under normal feeding conditions, glycine is not adequately synthesized in birds or in other animals, particularly in a diseased state. Glycine degradation occurs through three pathways: the glycine cleavage system (GCS), serine hydroxymethyltransferase, and conversion to glyoxylate by peroxisomal d-amino acid oxidase. Among these pathways, GCS is the major enzyme to initiate glycine degradation to form ammonia and CO2 in animals. In addition, glycine is utilized for the biosynthesis of glutathione, heme, creatine, nucleic acids, and uric acid. Furthermore, glycine is a significant component of bile acids secreted into the lumen of the small intestine that is necessary for the digestion of dietary fat and the absorption of long-chain fatty acids. Glycine plays an important role in metabolic regulation, anti-oxidative reactions, and neurological function. Thus, this nutrient has been used to: (1) prevent tissue injury; (2) enhance anti-oxidative capacity; (3) promote protein synthesis and wound healing; (4) improve immunity; and (5) treat metabolic disorders in obesity, diabetes, cardiovascular disease, ischemia-reperfusion injuries, cancers, and various inflammatory diseases. These multiple beneficial effects of glycine, coupled with its insufficient de novo synthesis, support the notion that it is a conditionally essential and also a functional amino acid for mammals (including pigs and humans).


Glycine Synthesis Metabolism Function Nutrition 



Alanineglyoxylate aminotransferase


Glycine cleavage enzyme system


Glycine receptor






Serine hydroxymethyltransferase


Threonine dehydrogenase



Work in our laboratories was supported by the National Basic Research Program of China (Grant 2013CB127302), National Research Initiative Competitive Grants from the Animal Reproduction Program (2008-35203-19120) and Animal Growth & Nutrient Utilization Program (2008-35206-18764) of the USDA National Institute of Food and Agriculture, AHA (10GRNT4480020), Texas A&M AgriLife Research (H-8200), the National Natural Science Foundation of China (No. u0731001, 30810103902, 30928018, 30972156, 31172217 and 31272450), China Postdoctoral Science Foundation (2012T50163), Chinese Universities Scientific Funds (No. 2012RC024), and the Thousand-People Talent program at China Agricultural University. Important contributions of our graduate students and colleagues to the recent development of the field are gratefully appreciated.

Conflict of interest

The authors declare that they have no conflict of interests.


  1. Alvarado-Vasquez N, Zamudio P, Ceron E et al (2003) Effect of glycine in streptozotocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol 134:521–527PubMedCrossRefGoogle Scholar
  2. Amin K, Li J, Chao WR et al (2003) Dietary glycine inhibits angiogenesis during wound healing and tumor growth. Cancer Biol Ther 2:173–178PubMedGoogle Scholar
  3. Arnstein HR, Keglevic D (1956) A comparison of alanine and glucose as precursors of serine and glycine. Biochem J 62:199–205PubMedGoogle Scholar
  4. Arnstein HR, Neuberger A (1953) The synthesis of glycine and serine by the rat. Biochem J 55:271–280PubMedGoogle Scholar
  5. Ascher E, Hanson JN, Cheng W et al (2001) Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury. Surgery 129:231–235PubMedCrossRefGoogle Scholar
  6. Bahmani F, Bathaie SZ, Aldavood SJ et al (2012) Glycine therapy inhibits the progression of cataract in streptozotocin-induced diabetic rats. Mol Vis 18:439–448PubMedGoogle Scholar
  7. Baker DH (2009) Advances in protein-amino acid nutrition of poultry. Amino Acids 37:29–41PubMedCrossRefGoogle Scholar
  8. Ballèvre O, Cadenhead A, Calder AG et al (1990) Quantitative partition of threonine oxidation in pigs: effect of dietary threonine. Am J Physiol 259:E483–E491PubMedGoogle Scholar
  9. Ballèvre O, Buchan V, Rees WD et al (1991) Sarcosine kinetics in pigs by infusion of [1-14C]sarcosine: use for refining estimates of glycine and threonine kinetics. Am J Physiol 260:E662–E668PubMedGoogle Scholar
  10. Bannai M, Kawai N (2012) New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci 118:145–148PubMedCrossRefGoogle Scholar
  11. Barness LA, Opitz JM, Gilbert-Barness E (2007) Obesity: genetic, molecular, and environmental aspects. Am J Med Genet A 143A:3016–3034PubMedCrossRefGoogle Scholar
  12. Bergeron F, Otto A, Blache P et al (1998) Molecular cloning and tissue distribution of rat sarcosine dehydrogenase. Eur J Biochem 257:556–561PubMedCrossRefGoogle Scholar
  13. Bird MI, Nunn PB (1983) Metabolic homoeostasis of l-threonine in the normally-fed rat. Importance of liver threonine dehydrogenase activity. Biochem J 214:687–694PubMedGoogle Scholar
  14. Brawley L, Torrens C, Anthony FW et al (2004) Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy. J Physiol 554:497–504PubMedCrossRefGoogle Scholar
  15. Brosnan JT, Wijekoon EP, Warford-Woolgar L et al (2009) Creatine synthesis is a major metabolic process in neonatal piglets and has important implications for amino acid metabolism and methyl balance. J Nutr 139:1292-1297Google Scholar
  16. Carvajal Sandoval G, Medina Santillan R et al (1999) Effect of glycine on hemoglobin glycation in diabetic patients. Proc West Pharmacol Soc 42:31–32PubMedGoogle Scholar
  17. Cetin I, Marconi AM, Baggiani AM et al (1995) In vivo placental transport of glycine and leucine in human pregnancies. Pediatr Res 37:571–575PubMedCrossRefGoogle Scholar
  18. Chao FC, Delwiche CC, Greenberg DM (1953) Biological precursors of glycine. Biochim Biophys Acta 10:103–109PubMedCrossRefGoogle Scholar
  19. Collard CD, Gelman S (2001) Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 94:1133–1138PubMedCrossRefGoogle Scholar
  20. Conter C, Rolland MO, Cheillan D et al (2006) Genetic heterogeneity of the GLDC gene in 28 unrelated patients with glycine encephalopathy. J Inherit Metab Dis 29:135–142PubMedCrossRefGoogle Scholar
  21. Corzo A, Kidd MT, Burnham DJ et al (2004) Dietary glycine needs of broiler chicks. Poult Sci 83:1382–1384PubMedGoogle Scholar
  22. Cruz M, Maldonado-Bernal C, Mondragon-Gonzalez R et al (2008) Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes. J Endocrinol Invest 31:694–699PubMedGoogle Scholar
  23. Dai ZL, Zhang J, Wu G, Zhu WY (2010) Utilization of amino acids by bacteria from the pig small intestine. Amino Acids 39:1201–1215PubMedCrossRefGoogle Scholar
  24. Dai ZL, Wu G, Zhu WY (2011) Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci 16:1768–1786CrossRefGoogle Scholar
  25. Dai ZL, Li XL, Xi PB et al (2012) Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids 42:1597–1608PubMedCrossRefGoogle Scholar
  26. Dai ZL, Wu ZL, Yang Y et al (2013) Nitric oxide and energy metabolism in mammals. BioFactors. doi: 10.1002/biof.1099 PubMedGoogle Scholar
  27. Dale RA (1978) Catabolism of threonine in mammals by coupling of l-threonine 3-dehydrogenase with 2-amino-3-oxobutyrate-CoA ligase. Biochim Biophys Acta 544:496–503PubMedCrossRefGoogle Scholar
  28. Danpure CJ (1997) Variable peroxisomal and mitochondrial targeting of alanine: glyoxylate aminotransferase in mammalian evolution and disease. BioEssays 19:317–326PubMedCrossRefGoogle Scholar
  29. Danpure CJ, Jennings PR (1986) Peroxisomal alanine:glyoxylate aminotransferase deficiency in primary hyperoxaluria type I. FEBS Lett 201:20–24PubMedCrossRefGoogle Scholar
  30. Danpure CJ, Cooper PJ, Wise PJ et al (1989) An enzyme trafficking defect in two patients with primary hyperoxaluria type 1: peroxisomal alanine/glyoxylate aminotransferase rerouted to mitochondria. J Cell Biol 108:1345–1352PubMedCrossRefGoogle Scholar
  31. Danpure CJ, Guttridge KM, Fryer P et al (1990) Subcellular distribution of hepatic alanine:glyoxylate aminotransferase in various mammalian species. J Cell Sci 97:669–678PubMedGoogle Scholar
  32. Darling PB, Dunn M, Sarwar G et al (1999) Threonine kinetics in preterm infants fed their mothers’ milk or formula with various ratios of whey to casein. Am J Clin Nutr 69:105–114PubMedGoogle Scholar
  33. Darling PB, Grunow J, Rafii M et al (2000) Threonine dehydrogenase is a minor degradative pathway of threonine catabolism in adult humans. Am J Physiol 278:E877–E884Google Scholar
  34. Dasarathy S, Kasumov T, Edmison JM et al (2009) Glycine and urea kinetics in nonalcoholic steatohepatitis in human: effect of intralipid infusion. Am J Physiol 297:G567–G575Google Scholar
  35. Davis AJ, Austic RE (1994) Dietary threonine imbalance alters threonine dehydrogenase activity in isolated hepatic mitochondria of chicks and rats. J Nutr 124:1667–1677PubMedGoogle Scholar
  36. Davis TA, Nguyen HV, Garciaa-Bravo R et al (1994) Amino acid composition of human milk is not unique. J Nutr 124:1126–1132PubMedGoogle Scholar
  37. de Aguiar Picanco E, Lopes-Paulo F, Marques RG et al (2011) l-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats. Int J Colorectal Dis 26:561–568PubMedCrossRefGoogle Scholar
  38. de Koning TJ, Snell K, Duran M et al (2003) l-serine in disease and development. Biochem J 371:653–661PubMedCrossRefGoogle Scholar
  39. Despres JP, Moorjani S, Lupien PJ et al (1990) Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 10:497–511PubMedCrossRefGoogle Scholar
  40. Donini S, Ferrari M, Fedeli C et al (2009) Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism. Biochem J 422:265–272PubMedCrossRefGoogle Scholar
  41. Donovan SM, Mar MH, Zeisel SH (1997) Choline and choline ester concentrations in porcine milk throughout lactation. J Nutr Biochem 8:603–607CrossRefGoogle Scholar
  42. dos Santos Fagundes I, Rotta LN, Schweigert ID et al (2001) Glycine, serine, and leucine metabolism in different regions of rat central nervous system. Neurochem Res 26:245–249CrossRefGoogle Scholar
  43. El Hafidi M, Perez I, Zamora J et al (2004) Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. Am J Physiol Regul Integr Comp Physiol 287:R1387–R1393PubMedCrossRefGoogle Scholar
  44. Estacion M, Weinberg JS, Sinkins WG et al (2003) Blockade of maitotoxin-induced endothelial cell lysis by glycine and l-alanine. Am J Physiol 284:C1006–C1020CrossRefGoogle Scholar
  45. Felig P, Marliss E, Cahill GF Jr (1969) Plasma amino acid levels and insulin secretion in obesity. N Engl J Med 281:811–816PubMedCrossRefGoogle Scholar
  46. Finkelstein JD, Martin JJ, Harris BJ et al (1982) Regulation of the betaine content of rat liver. Arch Biochem Biophys 218:169–173PubMedCrossRefGoogle Scholar
  47. Flynn NE, Knabe DA, Mallick BK et al (2000) Postnatal changes of plasma amino acids in suckling pigs. J Anim Sci 78:2369–2375PubMedGoogle Scholar
  48. Gannon MC, Nuttall JA, Nuttall FQ (2002) The metabolic response to ingested glycine. Am J Clin Nutr 76:1302–1307PubMedGoogle Scholar
  49. Gao HJ, Wu G, Spencer TE et al (2009) Select nutrients in the ovine uterine lumen: I. Amino acids, glucose and ions in uterine lumenal flushings of cyclic and pregnant ewes. Biol Reprod 80:86–93PubMedCrossRefGoogle Scholar
  50. Garcia-Macedo R, Sanchez-Munoz F, Almanza-Perez JC et al (2008) Glycine increases mRNA adiponectin and diminishes pro-inflammatory adipokines expression in 3T3-L1 cells. Eur J Pharmacol 587:317–321PubMedCrossRefGoogle Scholar
  51. Geng MM, Li TJ, Kong XF et al (2011) Reduced expression of intestinal N-acetylglutamate synthase in suckling piglets: a novel molecular mechanism for arginine as a nutritionally essential amino acid for neonates. Amino Acids 40:1513–1522PubMedCrossRefGoogle Scholar
  52. Girgis S, Nasrallah IM, Suh JR et al (1998) Molecular cloning, characterization and alternative splicing of the human cytoplasmic serine hydroxymethyltransferase gene. Gene 210:315–324PubMedCrossRefGoogle Scholar
  53. Guay F, Matte JJ, Girard CL et al (2002) Effect of folic acid and glycine supplementation on embryo development and folate metabolism during early pregnancy in pigs. J Anim Sci 80:2134–2143PubMedGoogle Scholar
  54. Hafkenscheid JC, Hectors MP (1975) An enzymic method for the determination of the glycine/taurine ratio of conjugated bile acid in bile. Clin Chim Acta 65:67–74PubMedCrossRefGoogle Scholar
  55. Hall JC (1998) Glycine. JPEN J Parenter Enteral Nutr 22:393–398PubMedCrossRefGoogle Scholar
  56. Hammer VA, Rogers QR, Freedland RA (1996) Threonine is catabolized by l-threonine 3-dehydrogenase and threonine dehydratase in hepatocytes from domestic cats (Felis domestica). J Nutr 126:2218–2226PubMedGoogle Scholar
  57. Harada E, Kiriyama H, Kobayashi E et al (1988) Postnatal development of biliary and pancreatic exocrine secretion in piglets. Comp Biochem Physiol A 91:43–51PubMedCrossRefGoogle Scholar
  58. Hartshorne D, Greenberg DM (1964) Studies on liver threonine dehydrogenase. Arch Biochem Biophys 105:173–178PubMedCrossRefGoogle Scholar
  59. Hasegawa S, Ichiyama T, Sonaka I et al (2012) Cysteine, histidine and glycine exhibit anti-inflammatory effects in human coronary arterial endothelial cells. Clin Exp Immunol 167:269–274PubMedCrossRefGoogle Scholar
  60. Hellwing ALF, Tauson AH, Skrede A et al (2007) Bacterial protein meal in diets for pigs and minks: comparative studies on protein turnover rate and urinary excretion of purine base derivatives. Arch Anim Nutr 61:425–443PubMedCrossRefGoogle Scholar
  61. Holmes RP, Assimos DG (1998) Glyoxylate synthesis, and its modulation and influence on oxalate synthesis. J Urol 160:1617–1624PubMedCrossRefGoogle Scholar
  62. House JD, Hall BN, Brosnan JT (2001) Threonine metabolism in isolated rat hepatocytes. Am J Physiol Endocrinol Metab 281:E1300–E1307PubMedGoogle Scholar
  63. Huxley RR, Shiell AW, Law CM (2000) The role of size at birth and postnatal catch-up growth in determining systolic blood pressure: a systematic review of the literature. J Hypertens 18:815–831PubMedCrossRefGoogle Scholar
  64. Ikejima K, Iimuro Y, Forman DT et al (1996) A diet containing glycine improves survival in endotoxin shock in the rat. Am J Physiol 271:G97–G103PubMedGoogle Scholar
  65. Ikejima K, Qu W, Stachlewitz RF et al (1997) Kupffer cells contain a glycine-gated chloride channel. Am J Physiol 272:G1581–G1586PubMedGoogle Scholar
  66. Ito K, Ozasa H, Noda Y et al (2008) Effect of non-essential amino acid glycine administration on the liver regeneration of partially hepatectomized rats with hepatic ischemia/reperfusion injury. Clin Nutr 27:773–780PubMedCrossRefGoogle Scholar
  67. Jackson AA (1991) The glycine story. Eur J Clin Nutr 45:59–65PubMedGoogle Scholar
  68. Jackson AA, Persaud C, Hall M et al (1997) Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants. Arch Dis Child Fetal Neonatal Ed 76:F152–F157PubMedCrossRefGoogle Scholar
  69. Jackson AA, Dunn RL, Marchand MC et al (2002) Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Clin Sci (Lond) 103:633–639Google Scholar
  70. Jacob T, Ascher E, Hingorani A et al (2003) Glycine prevents the induction of apoptosis attributed to mesenteric ischemia/reperfusion injury in a rat model. Surgery 134:457–466PubMedCrossRefGoogle Scholar
  71. Jois M, Hall B, Fewer K et al (1989) Regulation of hepatic glycine catabolism by glucagon. J Biol Chem 264:3347–3351PubMedGoogle Scholar
  72. Kikuchi G, Motokawa Y, Yoshida T et al (2008) Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia. Proc Jpn Acad Ser B 84:246–263CrossRefGoogle Scholar
  73. Kristensen NB, Norgaard JV, Wamberg S et al (2009) Absorption and metabolism of benzoic acid in growing pigs. J Anim Sci 87:2815–2822PubMedCrossRefGoogle Scholar
  74. Lamers Y, Williamson J, Gilbert LR et al (2007) Glycine turnover and decarboxylation rate quantified in healthy men and women using primed, constant infusions of [1,2–13C2]glycine and [2H3]leucine. J Nutr 137:2647–2652PubMedGoogle Scholar
  75. Le Floc’h N, Obled C, Sève B (1995) In vivo threonine oxidation rate is dependent on threonine dietary supply in growing pigs fed low to adequate levels. J Nutr 125:2550–2562PubMedGoogle Scholar
  76. Lee IS, Muragaki Y, Ideguchi T et al (1995) Molecular cloning and sequencing of a cDNA encoding alanine-glyoxylate aminotransferase 2 from rat kidney. J Biochem 117:856–862PubMedCrossRefGoogle Scholar
  77. Lehninger A, Nelson DL, Cox MM (1993) Principles of biochemistry, 2nd edn. Worth Publishers, New York, p 526Google Scholar
  78. Lewis AJ (2001) Amino acids in swine nutrition. In: Lewis AJ, Southern L (eds) Swine nutrition, 2nd edn. CRC Press, New York, pp 131–150Google Scholar
  79. Lewis RM, Godfrey KM, Jackson AA et al (2005) Low serine hydroxymethyltransferase activity in the human placenta has important implications for fetal glycine supply. J Clin Endocrinol Metab 90:1594–1598PubMedCrossRefGoogle Scholar
  80. Li X, Bradford BU, Wheeler MD et al (2001) Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Infect Immun 69:5883–5891PubMedCrossRefGoogle Scholar
  81. Li P, Yin YL, Li DF et al (2007) Amino acids and immune function. Br J Nutr 98:237–252PubMedCrossRefGoogle Scholar
  82. Li XL, Rezaei R, Li et al (2011) Composition of amino acids in feed ingredients for animal diets.  Amino Acids 40:1159-1168Google Scholar
  83. Lowry M, Hall DE, Brosnan JT (1985a) Hydroxyproline metabolism by the rat kidney: distribution of renal enzymes of hydroxyproline catabolism and renal conversion of hydroxyproline to glycine and serine. Metabolism 34:955–961PubMedCrossRefGoogle Scholar
  84. Lowry M, Hall DE, Brosnan JT (1985b) Increased activity of renal glycine-cleavage-enzyme complex in metabolic acidosis. Biochem J 231:477–480PubMedGoogle Scholar
  85. MacFarlane AJ, Liu X, Perry CA et al (2008) Cytoplasmic serine hydroxymethyltransferase regulates the metabolic partitioning of methylenetetrahydrofolate but is not essential in mice. J Biol Chem 283:25846–25853PubMedCrossRefGoogle Scholar
  86. Matilla B, Mauriz JL, Culebras JM et al (2002) Glycine: a cell-protecting anti-oxidant nutrient. Nutr Hosp 17:2–9PubMedGoogle Scholar
  87. Matrone G, Thomason EL Jr, Burn CR (1960) Requirement and utilization of iron by the baby pig. J Nutr 72:459–465PubMedGoogle Scholar
  88. Matthews DE, Conway JM, Young VR et al (1981) Glycine nitrogen metabolism in man. Metabolism 30:886–893PubMedCrossRefGoogle Scholar
  89. Mavromichalis I, Parr TM, Gabert VM et al (2001) True ileal digestibility of amino acids in sow’s milk for 17-day-old pigs. J Anim Sci 79:707–713PubMedGoogle Scholar
  90. McCarty MF, Barroso-Aranda J, Contreras F (2009) The hyperpolarizing impact of glycine on endothelial cells may be anti-atherogenic. Med Hypotheses 73:263–264PubMedCrossRefGoogle Scholar
  91. Meister A (1965) Biochemistry of amino acids. Academic Press, New YorkGoogle Scholar
  92. Melendez-Hevia E, De Paz-Lugo P, Cornish-Bowden A et al (2009) A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. J Biosci 34:853–872PubMedCrossRefGoogle Scholar
  93. Mertz ET, Beeson WM, Jackson HD (1952) Classification of essential amino acids for the weanling pig. Arch Biochem Biophys 38:121–128PubMedCrossRefGoogle Scholar
  94. Mudd SH, Cerone R, Schiaffino MC et al (2001) Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia. J Inherit Metab Dis 24:448–464PubMedCrossRefGoogle Scholar
  95. Narkewicz MR, Thureen PJ, Sauls SD et al (1996) Serine and glycine metabolism in hepatocytes from mid gestation fetal lambs. Pediatr Res 39:1085–1090PubMedCrossRefGoogle Scholar
  96. Neuman RE, Logan MA (1950) The determination of hydroxyproline. J Biol Chem 184:299–306PubMedGoogle Scholar
  97. Newsholme E, Leech T (2010) Functional biochemistry in health and disease. Wiley, West SussexGoogle Scholar
  98. Noguchi T, Takada Y (1979) Peroxisomal localization of alanine: glyoxylate aminotransferase in human liver. Arch Biochem Biophys 196:645–647PubMedCrossRefGoogle Scholar
  99. Noguchi T, Okuno E, Takada Y et al (1978) Characteristics of hepatic alanine-glyoxylate aminotransferase in different mammalian species. Biochem J 169:113–122PubMedGoogle Scholar
  100. Ogawa H, Gomi T, Fujioka M (2000) Serine hydroxymethyltransferase and threonine aldolase: are they identical? Int J Biochem Cell Biol 32:289–301PubMedCrossRefGoogle Scholar
  101. Olsson J, Sandfeldt L, Hahn RG (1997) Survival after high-dose intraperitoneal infusion of glycine solution in the mouse. Scand J Urol Nephrol 31:119–121PubMedCrossRefGoogle Scholar
  102. Pal PB, Pal S, Das J et al (2012) Modulation of mercury-induced mitochondria-dependent apoptosis by glycine in hepatocytes. Amino Acids 42:1669–1683PubMedCrossRefGoogle Scholar
  103. Paolini CL, Marconi AM, Ronzoni S et al (2001) Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J Clin Endocrinol Metab 86:5427–5432PubMedCrossRefGoogle Scholar
  104. Parimi PS, Gruca LL, Kalhan SC (2005) Metabolism of threonine in newborn infants. Am J Physiol Endocrinol Metab 289:E981–E985PubMedCrossRefGoogle Scholar
  105. Petrat F, Drowatzky J, Boengler K et al (2011) Protection from glycine at low doses in ischemia-reperfusion injury of the rat small intestine. Eur Surg Res 46:180–187PubMedCrossRefGoogle Scholar
  106. Pfeiffer F, Betz H (1981) Solubilization of the glycine receptor from rat spinal cord. Brain Res 226:273–279PubMedCrossRefGoogle Scholar
  107. Phang JM, Liu W, Hancock C (2013) Bridging epigenetics and metabolism: role of non-essential amino acids. Epigenetics 8(3):231–236PubMedCrossRefGoogle Scholar
  108. Porter DH, Cook RJ, Wagner C (1985) Enzymatic properties of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver. Arch Biochem Biophys 243:396–407PubMedCrossRefGoogle Scholar
  109. Powell S, Bidner TD, Payne RL et al (2011) Growth performance of 20- to 50-kilogram pigs fed low-crude-protein diets supplemented with histidine, cystine, glycine, glutamic acid, or arginine. J Anim Sci 89:3643–3650PubMedCrossRefGoogle Scholar
  110. Rajendra S, Lynch JW, Pierce KD et al (1995) Mutation of an arginine residue in the human glycine receptor transforms beta-alanine and taurine from agonists into competitive antagonists. Neuron 14:169–175PubMedCrossRefGoogle Scholar
  111. Rajendra S, Lynch JW, Schofield PR (1997) The glycine receptor. Pharmacol Ther 73:121–146PubMedCrossRefGoogle Scholar
  112. Ramakrishnan S, Sulochana KN (1993) Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis. Exp Eye Res 57:623–628PubMedCrossRefGoogle Scholar
  113. Rawn JD (1989) Biochemistry. Carolina Biological Supply, North Carolina, p 470Google Scholar
  114. Reeds PJ, Burrin DG, Stoll B et al (1997) Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed piglets. Am J Physiol 273:E408–E415PubMedGoogle Scholar
  115. Rezaei R, Wang WW, Wu ZL et al (2013a) Biochemical and physiological bases for utilization of dietary amino acids by young pigs. J Anim Sci Biotech 4:7CrossRefGoogle Scholar
  116. Rezaei R, Knabe DA, Tekwe CD et al (2013b) Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids 44:911–923PubMedCrossRefGoogle Scholar
  117. Rivera-Ferre MG, Aguilera JF, Nieto R (2006) Differences in whole-body protein turnover between Iberian and Landrace pigs fed adequate or lysine-deficient diets. J Anim Sci 84:3346–3355PubMedCrossRefGoogle Scholar
  118. Rodionov RN, Murry DJ, Vaulman SF et al (2010) Human alanine-glyoxylate aminotransferase 2 lowers asymmetric dimethylarginine and protects from inhibition of nitric oxide production. J Biol Chem 285:5385–5391PubMedCrossRefGoogle Scholar
  119. Rose ML, Cattley RC, Dunn C et al (1999a) Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643. Carcinogenesis 20:2075–2081PubMedCrossRefGoogle Scholar
  120. Rose ML, Madren J, Bunzendahl H et al (1999b) Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis 20:793–798PubMedCrossRefGoogle Scholar
  121. Ruiz-Torres A, Kurten I (1976) Is there a recycling of hydroxyproline? Experientia 32:555–556PubMedCrossRefGoogle Scholar
  122. Sandfeldt L, Riddez L, Rajs J et al (2001) High-dose intravenous infusion of irrigating fluids containing glycine and mannitol in the pig. J Surg Res 95:114–125PubMedCrossRefGoogle Scholar
  123. Sarkar U, Choudhuri MA (1981) Effects of some oxidants and antioxidants on senescence of isolated leaves of sunflower with special reference to glycolate content, glycolate oxidase, and catalase activities. Can J Botany 59:392-396Google Scholar
  124. Sato K, Yoshida S, Fujiwara K et al (1991) Glycine cleavage system in astrocytes. Brain Res 567:64–70PubMedCrossRefGoogle Scholar
  125. Satterfield MC, Dunlap KA, Keisler DH et al (2012) Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep. Amino Acids 43:1593–1603CrossRefGoogle Scholar
  126. Schadereit R, Krawielitzki K, Herrmann U (1986) 15N transamination in the administration of various tracer substances. 1. Whole body studies in rats. Arch Tierernahr 36:783–792PubMedCrossRefGoogle Scholar
  127. Schemmer P, Bradford BU, Rose ML et al (1999) Intravenous glycine improves survival in rat liver transplantation. Am J Physiol 276:G924–G932PubMedGoogle Scholar
  128. Schirch L, Gross T (1968) Serine transhydroxymethylase. Identification as the threonine and allothreonine aldolases. J Biol Chem 243:5651–5655PubMedGoogle Scholar
  129. Sekhar RV, McKay SV, Patel SG et al (2011) Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Diabetes Care 34:162–167PubMedCrossRefGoogle Scholar
  130. Shemin D (1946) The biological conversion of l-serine to glycine. J Biol Chem 162:297–307PubMedGoogle Scholar
  131. Shemin D (1950) Some aspects of the biosynthesis of amino acids. Cold Spring Harb Symp 14:161–167CrossRefGoogle Scholar
  132. Shoham S, Javitt DC, Heresco-Levy U (1999) High dose glycine nutrition affects glial cell morphology in rat hippocampus and cerebellum. Int J Neuropsychopharmacol 2:35–40PubMedCrossRefGoogle Scholar
  133. Shoham S, Javitt DC, Heresco-Levy U (2001) Chronic high-dose glycine nutrition: effects on rat brain cell morphology. Biol Psychiatry 49:876–885PubMedCrossRefGoogle Scholar
  134. Slomowitz LA, Gabbai FB, Khang SJ et al (2004) Protein intake regulates the vasodilatory function of the kidney and NMDA receptor expression. Am J Physiol Regul Integr Comp Physiol 287:R1184–R1189PubMedCrossRefGoogle Scholar
  135. Soloway S, Stetten D Jr (1953) The metabolism of choline and its conversion to glycine in the rats. J Biol Chem 204:207–214PubMedGoogle Scholar
  136. Sommer SP, Sommer S, Sinha B et al (2012) Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats. Interact Cardiovasc Thorac Surg 14:521–525PubMedCrossRefGoogle Scholar
  137. Spittler A, Reissner CM, Oehler R et al (1999) Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression. FASEB J 13:563–571PubMedGoogle Scholar
  138. Stachlewitz RF, Li X, Smith S et al (2000) Glycine inhibits growth of T lymphocytes by an IL-2-independent mechanism. J Immunol 164:176–182PubMedGoogle Scholar
  139. Stover PJ, Chen LH, Suh JR et al (1997) Molecular cloning, characterization, and regulation of the human mitochondrial serine hydroxymethyltransferase gene. J Biol Chem 272:1842–1848PubMedCrossRefGoogle Scholar
  140. Takada Y, Noguchi T (1982) Subcellular distribution, and physical and immunological properties of hepatic alanine: glyoxylate aminotransferase isoenzymes in different mammalian species. Comp Biochem Physiol B 72:597–604PubMedCrossRefGoogle Scholar
  141. Tariq M, Al Moutaery AR (1997) Studies on the antisecretory, gastric anti-ulcer and cytoprotective properties of glycine. Res Commun Mol Pathol Pharmacol 97:185–198PubMedGoogle Scholar
  142. Thompson JS, Richardson KE (1967) Isolation and characterization of an l-alanine: glyoxylate aminotransferase from human liver. J Biol Chem 242:3614–3619PubMedGoogle Scholar
  143. Thureen PJ, Narkewicz MR, Battaglia FC et al (1995) Pathways of serine and glycine metabolism in primary culture of ovine fetal hepatocytes. Pediatr Res 38:775–782PubMedCrossRefGoogle Scholar
  144. Trujillo ME, Scherer PE (2006) Adipose tissue-derived factors: impact on health and disease. Endocr Rev 27:762–778PubMedGoogle Scholar
  145. Vazquez A, Tedeschi PM, Bertino JR (2013) Overexpression of the mitochondrial folate and glycine-serine pathway: a new determinant of methotrexate selectivity in tumors. Cancer Res 73:478–482PubMedCrossRefGoogle Scholar
  146. Walsh DA, Sallach HJ (1966) Comparative studies on the pathways for serine synthesis in animal tissues. J Biol Chem 241:4068–4076PubMedGoogle Scholar
  147. Wang JJ, Wu ZL, Li DF et al (2012) Nutrition, epigenetics, and metabolic syndrome. Antioxid Redox Signal 17:282–301PubMedCrossRefGoogle Scholar
  148. Watts RWE, Crawhall JC (1959) The first glycine metabolic pool in man. Biochem J 73:277–286PubMedGoogle Scholar
  149. Wei JW, Carroll RJ, Harden KK et al (2012) Comparisons of treatment means when factors do not interact in two-factorial studies. Amino Acids 42:2031–2035PubMedCrossRefGoogle Scholar
  150. Wheeler MD, Ikejema K, Enomoto N et al (1999) Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci 56:843–856PubMedCrossRefGoogle Scholar
  151. Wheeler MD, Rose ML, Yamashima S et al (2000) Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. Am J Physiol 279:L390–L398Google Scholar
  152. Wijekoon EP, Skinner C, Brosnan ME et al (2004) Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes. Can J Physiol Pharmacol 82:506–514PubMedCrossRefGoogle Scholar
  153. Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17PubMedCrossRefGoogle Scholar
  154. Wu G (2010a) Recent advances in swine amino acid nutrition. J Anim Sci Biotech 1:49–61Google Scholar
  155. Wu G (2010b) Functional amino acids in growth, reproduction and health. Adv Nutr 1:31–37PubMedCrossRefGoogle Scholar
  156. Wu G (2013) Amino acids: biochemistry and nutrition. CRC Press, Boca RatonCrossRefGoogle Scholar
  157. Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424PubMedGoogle Scholar
  158. Wu G, Meininger CJ (2002) Regulation of nitric oxide synthesis by dietary factors. Annu Rev Nutr 22:61–86PubMedCrossRefGoogle Scholar
  159. Wu G, Borbolla AG, Knabe DA (1994) The uptake of glutamine and release of arginine, citrulline and proline by the small intestine of developing pigs. J Nutr 124:2437–2444PubMedGoogle Scholar
  160. Wu G, Meier SA, Knabe DA (1996) Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J Nutr 126:2578–2584PubMedGoogle Scholar
  161. Wu G, Knabe DA, Kim SW (2004a) Arginine nutrition in neonatal pigs. J Nutr 134:2783S–2790SPubMedGoogle Scholar
  162. Wu G, Fang YZ, Yang S et al (2004b) Glutathione metabolism and its implications for health. J Nutr 134:489–492PubMedGoogle Scholar
  163. Wu G, Bazer FW, Burghardt RC et al (2010) Functional amino acids in swine nutrition and production. In: Doppenberg J, van der Aar P (eds) Dynamics in animal nutrition. Wageningen Academic Publishers, The Netherlands, pp 69–98Google Scholar
  164. Wu G, Bazer FW, Burghardt RC et al (2011a) Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 40:1053–1063PubMedCrossRefGoogle Scholar
  165. Wu G, Bazer FW, Johnson GA et al (2011b) Important roles for l-glutamine in swine nutrition and production. J Anim Sci 89:2017–2030PubMedCrossRefGoogle Scholar
  166. Wu G, Imhoff-Kunsch B, Girard AW (2012) Biological mechanisms for nutritional regulation of maternal health and fetal development. Paediatr Perinat Epidemiol 26(Suppl 1):4–26PubMedCrossRefGoogle Scholar
  167. Wu G, Wu ZL, Dai ZL et al (2013) Dietary requirements of “nutritionally nonessential amino acids” by animals and humans. Amino Acids 44:1107–1113PubMedCrossRefGoogle Scholar
  168. Xue HH, Sakaguchi T, Fujie M et al (1999) Flux of the l-serine metabolism in rabbit, human, and dog livers. Substantial contributions of both mitochondrial and peroxisomal serine:pyruvate/alanine:glyoxylate aminotransferase. J Biol Chem 274:16028–16033PubMedCrossRefGoogle Scholar
  169. Yamashina S, Konno A, Wheeler MD et al (2001) Endothelial cells contain a glycine-gated chloride channel. Nutr Cancer 40:197–204PubMedCrossRefGoogle Scholar
  170. Yamashina S, Ikejima K, Enomoto N et al (2005) Glycine as a therapeutic immuno-nutrient for alcoholic liver disease. Alcohol Clin Exp Res 29(11 Suppl):162S–165SPubMedCrossRefGoogle Scholar
  171. Yamashina S, Ikejima K, Rusyn I et al (2007) Glycine as a potent anti-angiogenic nutrient for tumor growth. J Gastroenterol Hepatol 22(Suppl 1):S62–S64PubMedCrossRefGoogle Scholar
  172. Yan BX, Sun YQ (1997) Glycine residues provide flexibility for enzyme active sites. J Biol Chem 272:3190–3194PubMedCrossRefGoogle Scholar
  173. Yao K, Yin YL, Li XL et al (2012) Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells. Amino Acids 42:2491–2500PubMedCrossRefGoogle Scholar
  174. Yeo EJ, Wagner C (1994) Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci USA 91:210–214PubMedCrossRefGoogle Scholar
  175. Yeung YG (1986) l-threonine aldolase is not a genuine enzyme in rat liver. Biochem J 237:187–190PubMedGoogle Scholar
  176. Yin M, Zhong Z, Connor HD et al (2002) Protective effect of glycine on renal injury induced by ischemia-reperfusion in vivo. Am J Physiol Renal Physiol 282:F417–F423PubMedCrossRefGoogle Scholar
  177. Yu YM, Yang RD, Matthews DE et al (1985) Quantitative aspects of glycine and alanine nitrogen metabolism in postabsorptive young men: effects of level of nitrogen and dispensable amino acid intake. J Nutr 115:399–410PubMedGoogle Scholar
  178. Yue JT, Mighiu PI, Naples M et al (2012) Glycine normalizes hepatic triglyceride-rich VLDL secretion by triggering the CNS in high-fat fed rats. Circ Res 110:1345–1354PubMedCrossRefGoogle Scholar
  179. Zhang J, Blusztajn JK, Zeisel SH (1992) Measurement of the formation of betaine aldehyde and betaine in rat liver mitochondria by a high pressure liquid chromatography-radioenzymatic assay. Biochim Biophys Acta 1117:333–339PubMedCrossRefGoogle Scholar
  180. Zhang Y, Ikejima K, Honda H et al (2000) Glycine prevents apoptosis of rat sinusoidal endothelial cells caused by deprivation of vascular endothelial growth factor. Hepatology 32:542–546PubMedCrossRefGoogle Scholar
  181. Zhong Z, Jones S, Thurman RG (1996) Glycine minimizes reperfusion injury in a low-flow, reflow liver perfusion model in the rat. Am J Physiol 270:G332–G338PubMedGoogle Scholar
  182. Zhong Z, Enomoto N, Connor HD et al (1999) Glycine improves survival after hemorrhagic shock in the rat. Shock 12:54–62PubMedCrossRefGoogle Scholar
  183. Zhong Z, Wheeler MD, Li X et al (2003) l-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care 6:229–240PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.State Key Laboratory of Animal NutritionChina Agricultural UniversityBeijingChina
  2. 2.Department of Animal ScienceTexas A&M UniversityCollege StationUSA

Personalised recommendations