Amino Acids

, Volume 46, Issue 8, pp 2037–2045 | Cite as

Glycine is a nutritionally essential amino acid for maximal growth of milk-fed young pigs

  • Weiwei Wang
  • Zhaolai Dai
  • Zhenlong Wu
  • Gang Lin
  • Sichao Jia
  • Shengdi Hu
  • Sudath Dahanayaka
  • Guoyao Wu
Original Article


Analysis of amino acids in milk protein reveals a relatively low content of glycine. This study was conducted with young pigs to test the hypothesis that milk-fed neonates require dietary glycine supplementation for maximal growth. Fourteen-day-old piglets were allotted randomly into one of four treatments (15 piglets/treatment), representing supplementation with 0, 0.5, 1 or 2 % glycine (dry matter basis) to a liquid milk replacer. Food was provided to piglets every 8 h (3 times/day) for 2 weeks. Milk intake (32.0–32.5 g dry matter/kg body weight per day) did not differ between control and glycine-supplemented piglets. Compared with control piglets, dietary supplementation with 0.5, 1 and 2 % glycine increased (P < 0.05) plasma concentrations of glycine and serine, daily weight gain, and body weight without affecting body composition, while reducing plasma concentrations of ammonia, urea, and glutamine, in a dose-dependent manner. Dietary supplementation with 0.5, 1 and 2 % glycine enhanced (P < 0.05) small-intestinal villus height, glycine transport (measured using Ussing chambers), mRNA levels for GLYT1, and anti-oxidative capacity (indicated by increased concentrations of reduced glutathione and a decreased ratio of oxidized glutathione to reduced glutathione). These novel results indicate, for the first time, that glycine is a nutritionally essential amino acid for maximal protein accretion in milk-fed piglets. The findings not only enhance understanding of protein nutrition, but also have important implications for designing improved formulas to feed human infants, particularly low birth weight and preterm infants.


Glycine Milk replacer Growth Intestinal morphology Piglet 



Dry matter


Reduced glutathione


Oxidized glutathione


Krebs–Henseleit bicarbonate





We thank students in our laboratories for assistance in this research. This project was supported, in part, by the National Basic Research Program of China (2013CB127302), the National Natural Science Foundation of China (31172217 and 31272450), China Postdoctoral Science Foundation (2012T50163), the Chinese Universities Scientific Fund (2013RC002), the Program for New Century Excellent Talents in University (NCET-12-0522), the Program for Beijing Municipal Excellent Talents, National Research Initiative Competitive Grants from the Animal Growth and Nutrient Utilization Program (2008-35206-18764 and 2014-67015-21770) of the USDA National Institute of Food and Agriculture, and Texas A&M AgriLife Research (H-8200).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Cunha TJ (1977) Swine feeding and nutrition. Academic, New YorkGoogle Scholar
  2. Dai ZL, Wu ZL, Jia SC et al (2014) Analysis of amino acid composition in proteins of animal tissues and foods as pre-column o-phthaldialdehyde derivatives by HPLC with fluorescence detection. J Chromatogr B. doi: 10.1016/j.jchromb.2014.03.025
  3. Davis TA, Nguyen H, Garcia-Bravo R et al (1994) Amino acid composition in human milk. J Nutr 124:1126–1132PubMedGoogle Scholar
  4. 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 26:561–568CrossRefGoogle Scholar
  5. Ducroc R, Sakar Y, Fanjul C et al (2010) Luminal leptin inhibits l-glutamine transport in rat small intestine: involvement of ASCT2 and B0AT1. Am J Physiol Gastrointest Liver Physiol 299:G179–G185PubMedCentralPubMedCrossRefGoogle Scholar
  6. Fu WJ, Stromberg AJ, Viele K et al (2010) Statistics and bioinformatics in nutritional sciences: analysis of complex data in the era of systems biology. J Nutr Biochem 21:561–572PubMedCentralPubMedCrossRefGoogle Scholar
  7. Fuchs SA, Peeters-Scholte CM, de Barse MJ et al (2012) Increased concentrations of both NMDA receptor co-agonists d-serine and glycine in global ischemia: a potential novel treatment target for perinatal asphyxia. Amino Acids 43:355–363PubMedCentralPubMedCrossRefGoogle Scholar
  8. He LQ, Yang HS, Li TJ et al (2013a) Effects of dietary l-lysine intake on the intestinal mucosa and expression of CAT genes in weaned piglets. Amino Acids 45:383–391PubMedCrossRefGoogle Scholar
  9. He LQ, Yin YL, Li TJ et al (2013b) Use of the Ussing chamber technique to study nutrient transport by epithelial tissues. Front Biosci 18:1266–1274CrossRefGoogle Scholar
  10. Jobgen W, Fu WJ, Gao H et al (2009) High fat feeding and dietary l-arginine supplementation differentially regulate gene expression in rat white adipose tissue. Amino Acids 37:187–198PubMedCrossRefGoogle Scholar
  11. Kalhan SC (2013) One-carbon metabolism, fetal growth and long-term consequences. Nestle Nutr Inst Workshop Ser 74:127–138PubMedCrossRefGoogle Scholar
  12. Kawai N, Bannai M, Seki S et al (2012) Pharmacokinetics and cerebral distribution of glycine administered to rats. Amino Acids 42:2129–2137PubMedCrossRefGoogle Scholar
  13. Kim SW, Wu G (2004) Dietary arginine supplementation enhances the growth of milk-fed young pigs. J Nutr 134:625–630PubMedGoogle Scholar
  14. Lei J, Feng DY, Zhang YL et al (2012) Nutritional and regulatory role of branched-chain amino acids in lactation. Front Biosci 17:2725–2739CrossRefGoogle Scholar
  15. Lin G, Wang X, Wu G et al (2014) Improving amino acid nutrition to prevent intrauterine growth restriction in mammals. Amino Acids. doi: 10.1007/s00726-014-1725-z
  16. Minelli A, Conte C, Cacciatore I et al (2012) Molecular mechanism underlying the cerebral effect of Gly-Pro-Glu tripeptide bound to l-dopa in a Parkinson’s animal model. Amino Acids 43:1359–1367PubMedCrossRefGoogle Scholar
  17. 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
  18. 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
  19. Reeds PJ, Burrin DG, Stoll B et al (1997) Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed pigs. Am J Physiol 273:E408–E415PubMedGoogle Scholar
  20. Rezaei R, Knabe DA, Li XL et al (2011) Enhanced efficiency of milk utilization for growth in surviving low-birth-weight piglets. J Anim Sci Biotechnol 2:73–83Google Scholar
  21. Rezaei R, Knabe DA, Tekwe CD et al (2013) Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids 44:911–923PubMedCrossRefGoogle Scholar
  22. 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
  23. Satterfield MC, Dunlap KA, Keisler DH et al (2013) Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep. Amino Acids 45:489–499PubMedCrossRefGoogle Scholar
  24. Schemmer P, Zhong Z, Galli U et al (2013) Glycine reduces platelet aggregation. Amino Acids 44:925–931PubMedCrossRefGoogle Scholar
  25. Shemin D (1950) Some aspects of the biosynthesis of amino acids. Cold Spring Harb Symp Quant Biol 14:161–167PubMedCrossRefGoogle Scholar
  26. 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
  27. Tsune I, Ikejima K, Hirose M et al (2003) Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology 125:775–785PubMedCrossRefGoogle Scholar
  28. Tuchscherer M, Puppe B, Tuchscherer A et al (2000) Early identification of neonates at risk: traits of newborn piglets with respect to survival. Theriogenology 54:371–388PubMedCrossRefGoogle Scholar
  29. Wang JJ, Chen LX, Li P et al (2008) Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr 138:1025–1032PubMedCrossRefGoogle Scholar
  30. Wang WW, Qiao SY, Li DF (2009) Amino acids and gut function. Amino Acids 37:105–110PubMedCrossRefGoogle Scholar
  31. Wang W, Zeng X, Mao X et al (2010) Optimal dietary true ileal digestible threonine for supporting the mucosal barrier in small intestine of weanling pigs. J Nutr 140:981–986PubMedCrossRefGoogle Scholar
  32. Wang JJ, Wu ZL, Li DF et al (2012) Nutrition, epigenetics, and metabolic syndrome. Antioxid Redox Signal 17:282–301PubMedCentralPubMedCrossRefGoogle Scholar
  33. Wang W, Wu Z, Dai Z et al (2013) Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids 45:463–477PubMedCrossRefGoogle Scholar
  34. Wei JW, Carroll RJ, Harden KK et al (2012) Comparisons of treatment means when factors do not interact in two-factorial studies. Amino Acids 42:2031–2035PubMedCentralPubMedCrossRefGoogle Scholar
  35. Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17PubMedCrossRefGoogle Scholar
  36. Wu G (2010) Functional amino acids in growth, reproduction and health. Adv Nutr 1:31–37PubMedCentralPubMedCrossRefGoogle Scholar
  37. Wu G (2013a) Amino acids: biochemistry and nutrition. CRC, Boca RatonCrossRefGoogle Scholar
  38. Wu G (2013b) Functional amino acids in nutrition and health. Amino Acids 45:407–411PubMedCrossRefGoogle Scholar
  39. Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424PubMedGoogle Scholar
  40. Wu G, Meininger CJ (2008) Analysis of citrulline, arginine, and methylarginines using high-performance liquid chromatography. Methods Enzymol 440:177–189PubMedCrossRefGoogle Scholar
  41. 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
  42. Wu G, Knabe DA, Yan W et al (1995) Glutamine and glucose metabolism in enterocytes of the neonatal pig. Am J Physiol Regulatory Integr Comp Physiol 268:R334–R342Google Scholar
  43. Wu G, Davis PK, Flynn NE et al (1997) Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs. J Nutr 127:2342–2349PubMedGoogle Scholar
  44. Wu G, Ott TL, Knabe DA et al (1999) Amino acid composition of the fetal pig. J Nutr 129:1031–1038PubMedGoogle Scholar
  45. Wu G, Bazer FW, Cudd TA et al (2004) Maternal nutrition and fetal development. J Nutr 134:2169–2172PubMedGoogle Scholar
  46. 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
  47. Wu G, Bazer FW, Dai ZL et al (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2:387–417CrossRefGoogle Scholar
  48. Yin J, Ren WK, Duan JL et al (2014) Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs. Amino Acids 46:883–892PubMedCrossRefGoogle Scholar
  49. Zhang J, Yin YL, Shu XG et al (2013) Oral administration of MSG increases expression of glutamate receptors and transporters in the gastrointestinal tract of young piglets. Amino Acids 45:1169–1177PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Weiwei Wang
    • 1
    • 2
  • Zhaolai Dai
    • 1
  • Zhenlong Wu
    • 1
  • Gang Lin
    • 1
    • 2
  • Sichao Jia
    • 2
  • Shengdi Hu
    • 2
  • Sudath Dahanayaka
    • 2
  • Guoyao Wu
    • 1
    • 2
  1. 1.State Key Laboratory of Animal NutritionChina Agricultural UniversityBeijingChina
  2. 2.Department of Animal ScienceTexas A&M UniversityCollege StationUSA

Personalised recommendations