Based on growth or nitrogen balance, amino acids (AA) had traditionally been classified as nutritionally essential (indispensable) or non-essential (dispensable) for animals and humans. Nutritionally essential AA (EAA) are defined as either those AA whose carbon skeletons cannot be synthesized de novo in animal cells or those that normally are insufficiently synthesized de novo by the animal organism relative to its needs for maintenance, growth, development, and health and which must be provided in the diet to meet requirements. In contrast, nutritionally non-essential AA (NEAA) are those AA which can be synthesized de novo in adequate amounts by the animal organism to meet requirements for maintenance, growth, development, and health and, therefore, need not be provided in the diet. Although EAA and NEAA had been described for over a century, there are no compelling data to substantiate the assumption that NEAA are synthesized sufficiently in animals and humans to meet the needs for maximal growth and optimal health. NEAA play important roles in regulating gene expression, cell signaling pathways, digestion and absorption of dietary nutrients, DNA and protein synthesis, proteolysis, metabolism of glucose and lipids, endocrine status, men and women fertility, acid–base balance, antioxidative responses, detoxification of xenobiotics and endogenous metabolites, neurotransmission, and immunity. Emerging evidence indicates dietary essentiality of “nutritionally non-essential amino acids” for animals and humans to achieve their full genetic potential for growth, development, reproduction, lactation, and resistance to metabolic and infectious diseases. This concept represents a new paradigm shift in protein nutrition to guide the feeding of mammals (including livestock), poultry, and fish.
RoseWC. The amino acid requirements of adult man. Nutr Abstr Rev Ser Hum Exp1957; 27: 631–47.
4.
RoseWC. The sequence of events leading to the establishment of the amino acid needs of man. Am J Public Health1968; 58: 2020–7.
5.
ReedsPJ. Dispensable and indispensable amino acids for humans. J Nutr2000; 130: 1835S–40S.
6.
BakerDH. Advances in protein-amino acid nutrition of poultry. Amino Acids2009; 37: 29–41.
7.
AbderhaldenE. Experiment on the feeding with completely degraded nutrition substances. Z Physiol Chem1912; 77: 22–58.
8.
RoseWCCoxGJ. The relation of arginine and histidine to growth. J Biol Chem1924; 61: 747–73.
9.
Institute of Medicine. Dietary reference intakes for energy, carbohydrates, fiber, fat, fatty acids, cholesterol, proteins, and amino acids, Washington, DC: The National Academies Press, 2005.
10.
MorrisonFB. Feeds and feeding, 22nd ed. Ithaca, NY: The Morrison Publishing Company, 1956.
11.
MaynardLALoosliJKHintzHFWarnerRG. Animal nutrition, 7th ed. New York: McGraw-Hill Book Company, 1979.
12.
CramptonEWHarrisLE. Applied animal nutrition, 2nd ed. San Francisco: W.H. Freeman and Company, 1969.
13.
National Research Council. Nutrient requirements of swine, Washington, DC: National Academy Press, 2012.
14.
WuGWuZLDaiZLYangYWangWWLiuCWangBWangJJYinYL. Dietary requirements of “nutritionally nonessential amino acids” by animals and humans. Amino Acids2013; 44: 1107–13.
15.
KalhanSCHansonRW. Resurgence of serine: an often neglected but indispensable amino acid. J Biol Chem2012; 287: 19786–91.
16.
PhangJMLiuWHancockC. Bridging epigenetics and metabolism: role of non-essential amino acids. Epigenetics2013; 8: 231–6.
17.
WuGBazerFWDaiZLLiDFWangJJWuZL. Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci2014; 2: 387–417.
18.
LiXBazerFWGaoHJobgenWJohnsonGALiPMcKnightJRSatterfieldMCSpencerTEWuG. Amino acids and gaseous signaling. Amino Acids2009; 37: 65–78.
19.
BrosnanJTBrosnanME. Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr2007; 27: 241–61.
20.
DahlNPiggMRistoffEGaliRCarlssonBMannervikBLarssonABoardP. Missense mutations in the human glutathione synthetase gene result in severe metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and neurological dysfunction. Hum Mol Genet1997; 6: 1147–52.
WangJJChenLXLiPLiXLZhouHJWangFLLiDFYinYLWuG. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr2008; 138: 1025–32.
23.
JobgenWFuWJGaoHLiPMeiningerCJSmithSBSpencerTEWuG. High fat feeding and dietary L-arginine supplementation differentially regulate gene expression in rat white adipose tissue. Amino Acids2009; 37: 187–98.
24.
LiuXDWuXYinYLLiuYQGengMMYangHSBlachierFWuGY. Effects of dietary L-arginine or N-carbamylglutamate supplementation during late gestation of sows on the miR-15b/16, miR-221/222, VEGFA and eNOS expression in umbilical vein. Amino Acids2012; 42: 2111–9.
25.
WangWWWuZLLinGHuSDWangBDaiZLWuG. Glycine stimulates protein synthesis and inhibits oxidative stress in pig small-intestinal epithelial cells. J Nutr2014; 144: 1540–8.
26.
RhoadsJMNiuXMSurendranSLiuYYWuG. Arginine stimulates cdx2-transformed intestinal epithelial cell migration via a mechanism requiring both nitric oxide and p70s6k signaling. J Nutr2008; 138: 1652–7.
27.
WangXQFrankJWXuJDunlapKASatterfieldMCBurghardtRCRomeroJJHansenTRWuGBazerFW. Functional role of arginine during the peri-implantation period of pregnancy. II. Consequences of loss of function of nitric oxide synthase NOS3 mRNA in ovine conceptus trophectoderm. Biol Reprod2014; 91: 1–10.
28.
YaoKYinYLChuWYLiuZQDengDLiTJHuangRLZhangJSTanBEWangWWuG. Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J Nutr2008; 138: 867–872.
29.
WangHZhangCWuGSunYLWangBHeBBDaiZLWuZL. Glutamine enhances tight-junction protein expression and modulates CRF signaling in the jejunum of weanling piglets. J Nutr2015; 145: 25–31.
30.
ZhangJYinYLShuXGLiTJLiFNTanBEWuZLWuG. Oral administration of MSG increases expression of glutamate receptors and transporters in the gastrointestinal tract of young piglets. Amino Acids2013; 45: 1169–77.
31.
San GabrielAUneyamaH. Amino acid sensing in the gastrointestinal tract. Amino Acids2013; 45: 451–61.
32.
DaiZLWuGZhuWY. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci2011; 16: 1768–86.
33.
WangWWDaiZLWuZLLinGJiaSCHuSDDahanayakaSWuG. Glycine is a nutritionally essential amino acid for maximal growth of milk-fed young pigs. Amino Acids2014; 46: 2037–45.
DaiZLLiXLXiPBZhangJWuGZhuWY. Regulatory role for L-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids2012; 43: 233–44.
36.
FuWJHaynesTEKohliRHuJShiWSpencerTECarrollRJMeiningerCJWuG. Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J Nutr2005; 135: 714–21.
37.
McKnightJRSatterfieldMCJobgenWSSmithSBSpencerTEMeiningerCJMcNealCJWuG. Beneficial effects of L-arginine on reducing obesity: potential mechanisms and important implications for human health. Amino Acids2010; 39: 349–57.
38.
JobgenWSFriedSKFuWJMeiningerCJWuG. Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem2006; 17: 571–88.
39.
WuZLSatterfieldMCBazerFWWuG. Regulation of brown adipose tissue development and white fat reduction by L-arginine. Curr Opin Clin Nutr Metab Care2012; 15: 529–38.
40.
TanBYinYLLiuZQLiXGXuHJKongXFHuangRLTangWJShinzatoISmithSBWuG. Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs. Amino Acids2009; 37: 169–75.
41.
HaynesTELiPLiXLShimotoriKSatoHFlynnNEWangJJKnabeDAWuG. L-Glutamine or L-alanyl-L-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Amino Acids2009; 37: 131–42.
42.
RezaeiRKnabeDATekweCDDahanayakaSFickenMDFielderSEEideSJLoveringSLWuG. Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids2013; 44: 911–23.
43.
KarnerCMEsenEOkunadeALPattersonBWLongF. Increased glutamine catabolism mediates bone anabolism in response to WNT signaling. J Clin Invest2015; 125: 551–62.
WuGFlynnNEFlynnSPJollyCADavisPK. Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats. J Nutr1999; 129: 1347–54.
46.
De JongeWJKwikkersKLTe VeldeAAVan DeventerSJHNolteMAMebiusRERuijterJMLamersMCLamersWH. Arginine deficiency affects early B cell maturation and lymphoid organ development in transgenic mice. J Clin Invest2002; 110: 1539–48.
47.
RenWKLiuSPChenSZhangFMLiNZYinJPengYYWuLLiuGYinYLWuG. Dietary L-glutamine supplementation increases Pasteurella multocida burden and expression of major virulence factors in mice. Amino Acids2013; 45: 947–55.
HäberleJGörgBRutschFSchmidtEToutainABenoistJFGelotASucALHöhneWSchliessFHäussingerDKochHG. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med2005; 353: 1926–33.
51.
WuGBazerFWDavisTAKimSWLiPRhoadsJMSatterfieldMCSmithSBSpencerTEYinYL. Arginine metabolism and nutrition in growth, health and disease. Amino Acids2009; 37: 153–68.
52.
NewsholmePAbdulkaderFRebelatoERomanattoTPinheiroCHVitzelKFSilvaEPBazotteRBProcopioJCuriRGorjaoRPithon-CuriTC. Amino acids and diabetes: implications for endocrine, metabolic and immune function. Front Biosci2011; 16: 315–39.
53.
LiCLiuCNissimIChenJChenPDolibaNZhangTNissimIDaikhinYStokesDYudkoffMBennettMJStanleyCAMatschinskyFMNajiA. Regulation of glucagon secretion in normal and diabetic human islets by γ-hydroxybutyrate and glycine. J Biol Chem2013; 288: 3938–51.
54.
HouYQWangLYiDWuG. N-acetylcysteine and intestinal health: a focus on mechanisms of its actions. Front Biosci2015; 20: 872–91.
BillardJM. D-Amino acids in brain neurotransmission and synaptic plasticity. Amino Acids2012; 43: 1851–60.
57.
RuzzoEKCapo-ChichiJMBen-ZeevBChitayatDMaoHPappasALHitomiYLuYFYaoXHamdanFFPelakKReznik-WolfHBar-JosephIOz-LeviDLevDLerman-SagieTLeshinsky-SilverEAniksterYBen-AsherEOlenderTColleauxLDécarieJCBlaserSBanwellBJoshiRBHeXPPatryLSilverRJDobrzenieckaSIslamMSHasnatASamuelsMEAryalDKRodriguizRMJiangYHWetselWCMcNamaraJORouleauGASilverDLLancetDPrasEMitchellGAMichaudJLGoldsteinDB. Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy. Neuron2013; 80: 429–41.
58.
CurthoysNPWatfordM. Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr1995; 15: 133–59.
59.
TaylorLCurthoysNP. Glutamine metabolism: role in acid-base balance. Biochem Mol Biol Educ2004; 32: 291–304.
60.
SturmRA. Molecular genetics of human pigmentation diversity. Hum Mol Genet2009; 18: R9–17.
MarlissEBAokiTTPozefskyTMostASCahillGFJr. Muscle and splanchnic glutamine and glutamate metabolism in postabsorptive and starved man. J Clin Invest1971; 50: 814–7.
63.
WuGMeiningerCJKnabeDABazerFWRhoadsJM. Arginine nutrition in development, health and disease. Curr Opin Clin Nutr Metab Care2000; 3: 59–66.
64.
GuedesRLMProsdocimiFFernandesGRMouraLKRibeiroHALOrtegaJM. Amino acids biosynthesis and nitrogen assimilation pathways: a great genomic deletion during eukaryote evolution. BMC Genomics2011; 12: S2–S2.
65.
HoltLEJrAlbaneseAA. Observations on amino acid deficiencies in man. Trans Assoc Am Physicians1944; 58: 143–56.
66.
MeisterA. Biochemistry of amino acids, New York: Academic Press, 1965.
67.
TanimuraJ. Studies on arginine in human semen. Part II. The effects of medication with L-arginine-HCl on male infertility. Bull Osaka Med School1967; 13: 84–9.
68.
Meléndez-HeviaEDe Paz-LugoPCornish-BowdenACárdenasML. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. J Biosci2009; 34: 853–72.
69.
SevastiadouSMalamitsi-PuchnerACostalosCSkouroliakouMBrianaDDAntsaklisARoma-GiannikouE. The impact of oral glutamine supplementation on the intestinal permeability and incidence of necrotizing enterocolitis/septicemia in premature neonates. J Matern Fetal Neonatal Med2011; 24: 1294–300.
70.
RogersQRChenDMHarperAE. The importance of dispensable amino acids for maximal growth in the rat. Proc Soc Exp Biol Med1970; 134: 517–22.
71.
BreuerLHJrPondWGWarnerRGLoosliJK. The role of dispensable amino acids in the nutrition of the rat. J Nutr1964; 82: 499–506.
72.
WomackM. Amino acid feeding studies: effects of various nonessential nitrogen sources and of added water. Proc Soc Exp Biol Med1969; 131: 977–9.
73.
StuckiWPHarperAE. Importance of dispensable amino acids for normal growth of chicks. J Nutr1961; 74: 377–83.
74.
MaruyamaKSundeMLHarperAE. Is L-glutamic acid nutritionally a dispensable amino acid for the young chick?Poultry Sci1976; 55: 45–60.
75.
WuGBazerFWJohnsonGAKnabeDABurghardtRCSpencerTELiXLWangJJ. Important roles for L-glutamine in swine nutrition and production. J Anim Sci2011; 89: 2017–30.
76.
LeiJFengDYZhangYLZhaoFQWuZLSan GabrielAFujishimaYUneyamaHWuG. Nutritional and regulatory role of branched-chain amino acids in lactation. Front Biosci2012; 17: 2725–39.
77.
DengDYinYLChuWYYaoKLiTJHuangRLLiuZQZhangJSWuG. Impaired translation initiation activation and reduced protein synthesis in weaned piglets fed a low-protein diet. J Nutr Biochem2009; 20: 544–52.
78.
DavisTAFiorottoML. Regulation of muscle growth in neonates. Curr Opin Nutr Metab Care2009; 12: 78–85.
79.
WuG. Dietary requirements of synthesizable amino acids by animals: a paradigm shift in protein nutrition. J Anim Sci Biotechnol2014; 5: 34–34.
80.
LiXLRezaeiRLiPWuG. Composition of amino acids in feed ingredients for animal diets. Amino Acids2011; 40: 1159–68.
81.
DaiZLWuZLJiaSCWuG. 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 B2014; 964: 116–27.
82.
HouYWangLZhangWYangZGDingBYZhuHLLiuYLQiuYSYinYLWuG. Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids2012; 43: 1233–42.
