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Amino acids are the building blocks of proteins in animals, including swine. With the development of new analytical methods and biochemical research, there is a growing interest in fundamental and applied studies to reexamine the roles and usage of amino acids (AAs) in swine production. In animal nutrition, AAs have been traditionally classified as nutritionally essential (EAAs) or nutritionally nonessential (NEAAs). AAs that are not synthesized de novo must be provided in diets. However, NEAAs synthesized by cells of animals are more abundant than EAAs in the body, but are not synthesized de novo in sufficient amounts for the maximal productivity or optimal health (including resistance to infectious diseases) of swine. This underscores the conceptual limitations of NEAAs in swine protein nutrition. Notably, the National Research Council (NRC 2012) has recognized both arginine and glutamine as conditionally essential AAs for pigs to improve their growth, development, reproduction, and lactation. Results of recent work have also provided compelling evidence for the nutritional essentiality of glutamate, glycine, and proline for young pigs. The inclusion of so-called NEAAs in diets can help balance AAs in diets, reduce the dietary levels of EAAs, and protect the small intestine from oxidative stress, while enhancing the growth performance, feed efficiency, and health of pigs. Thus, both EAAs and NEAAs are needed in diets to meet the requirements of pigs. This notion represents a new paradigm shift in our understanding of swine protein nutrition and is transforming pork production worldwide.

The liver plays a central role in amino acid (AA) metabolism in humans and other animals. In all mammals, this organ synthesizes many AAs (including glutamate, glutamine, alanine, aspartate, asparagine, glycine, serine, and homoarginine), glucose, and glutathione (a major antioxidant). Similar biochemical reactions occur in the liver of birds except for those for arginine and glutamine hydrolysis, proline oxidation, and gluconeogenesis from AAs. In contrast to mammals and birds, the liver of fish has high rates of glutamate and glutamine oxidation for ATP production. In most animals (except for cats and possibly some of the other carnivores), the liver produces taurine from methionine or cysteine. However, the activity of this pathway is limited in human infants (particularly preterm infants) and is also low in adult humans as compared with rats, birds and livestock species (e.g., pigs, cattle and sheep). The liver exhibits metabolic zonation and intracellular compartmentation for ureagenesis, uric acid synthesis, and gluconeogenesis, as well as AA degradation and syntheses. Capitalizing on these extensive bases of knowledge, dietary supplementation with functional AAs (e.g., methionine, N-acetylcysteine, and glycine) to humans and other animals can alleviate or prevent oxidative stress and damage in the liver. Because liver diseases are common problems in humans and farm animals (including fish), much research is warranted to further both basic and applied research on hepatic AA metabolism and functions.

Dietary polyamines and amino acids (AAs) are crucial for human growth, development, reproduction, and health. However, the scientific literature shows large variations in polyamine and AA concentrations among major staple foods of plant origin, and there is a scarcity of information regarding their complete composition of AAs. To provide a much-needed database, we quantified polyamines, agmatine, and AAs in select plant-source foods. On the dry matter basis, total polyamines were most abundant in corn grains, followed by soybeans, sweet potatoes, pistachio nuts, potatoes, peanuts, wheat flour and white rice in descending order. Glutamine was the most abundant AA in pistachio nuts, wheat flour and white rice, arginine in peanuts, leucine in corn grains, glutamate in soybeans, and asparagine in potatoes and sweet potatoes. Glutamine was the second most abundant AA in corn grains, peanuts, potatoes, and soybeans, arginine in pistachio nuts, proline in wheat flour, and glutamate in sweet potatoes and white rice. Free AAs represented ≤ 3.1% of total AAs in corn grains, peanuts, pistachio nuts, soybeans, wheat flour and white rice, but 34.4% and 28.5% in potatoes and sweet potatoes, respectively. Asparagine accounted for 32.3%, 17.5%, and 19.4% of total free AAs in potatoes, sweet potatoes, and white rice, respectively. The content of histidine, glycine, lysine, tryptophan, methionine, cysteine, and threonine was relatively low in corn grains, potatoes, sweet potatoes, and white rice. All of the analyzed plant-source foods lacked taurine, creatine, carnosine and anserine (antioxidants that are abundant in meats and also present in milk), and contained little 4-hydroxyproline. Proper proportions of plant- and animal-source products are likely most desirable for optimizing human nutrition and health.

The traditionally classified nutritionally non-essential amino acids are now known to be insufficiently synthesized for maximal growth and optimal health in piglets. This study determined the effects of dietary supplementation with an amino acid blend (AAB; glutamate:glutamine:glycine:arginine:N-acetylcysteine = 5:2:2:1:0.5) on piglet growth performance and intestinal functions. Sixteen piglets (24-day-old) were randomly assigned to a corn and soybean meal-based diet supplemented with 0.99% alanine (isonitrogenous control) or 1% AAB. On day 20 of the trial, blood and intestinal tissue samples were obtained from piglets. Compared with the control, AAB supplementation reduced (P < 0.05) diarrhoea incidence; plasma alanine aminotransferase and diamine oxidase activities; intestinal concentrations of hydrogen peroxide, malondialdehyde, and heat shock protein-70, and intestinal mRNA levels for interleukin-1β, interferon-γ, and chemokine (C-X-C motif) ligand-9; and the numbers of Enterobacterium family, Enterococcus genus and Clostridium coccoides in the colon digesta. Furthermore, AAB supplementation enhanced (P < 0.05): the plasma concentrations of serine, aspartate, glutamate, cysteine, tyrosine, phenylalanine, tryptophan, lysine, arginine, citrulline, ornithine, taurine, and γ-aminobutyric acid; intestinal villus height and surface area, villus height/crypt depth ratio, antioxidative enzyme activities, and mRNA levels for porcine β-defensin-1, sodium-independent amino acid transporters (b 0,+ AT and y + LAT1), aquaporin (AQP) 3, AQP8, AQP10, nuclear factor erythroid 2-related factor 2 and glutathione S-transferase omega-2, and protein abundances of AQP3, AQP4, claudin-1, occludin and myxovirus resistance 1; and the numbers of Bifidobacterium genus and Lactobacillus genus in the colon digesta. Collectively, these comprehensive results indicate that dietary AAB supplementation plays an important role in improving piglet growth and intestinal function.

Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering. Our interests have been using amino acids as therapeutics in pig and human disease models. Amino acids not only play an important role in protein biosynthesis, but also exert significant physiological effects in regulating immunity, anti-oxidation, redox regulation, energy metabolism, signal transduction, and animal behavior. Recent studies in pigs have shown that specific dietary amino acids can improve intestinal integrity and function under normal and pathological conditions that protect the host from different diseases. In this review, we summarize several pig models in intestinal diseases and how amino acids can be used as therapeutics in treating pig and human diseases.

Amino acids (AAs) are building blocks of protein. Eight AAs (Ala, Asn, Asp, Glu, Gln, Gly, Pro, and Ser) are formed by all animals, whereas de novo synthesis of Arg occurs in a species-specific manner in most mammals (e.g., humans, pigs, and rats). Synthesizable AAs were traditionally classified as nutritionally nonessential for animals, because they were thought to be formed in sufficient amounts. However, this assumption is not supported by evidence showing that 1) rats grow slowly when their diets do not contain Arg, Glu, or Gln despite adequate provision of all other proteinogenous AAs; 2) pigs cannot achieve maximum growth, lactation, or reproduction performance when fed corn- and soybean meal-based diets meeting National Research Council-recommended requirements of protein and AAs without supplemental Arg, Glu, Gln, Gly, or Pro; 3) chickens exhibit increases in lean tissue gain and feed efficiency when their diets are supplemented with Glu, Gln, Gly, and Pro; 4) lactating cows cannot obtain maximum milk protein production without a postruminal supply of Gln or Pro; 5) fish cannot achieve maximum growth when diets do not contain Gln or Pro; and 6) men fail to sustain spermatogenesis when fed an Arg-deficient diet. Quantitative analysis of nitrogen metabolism showed that AA synthesis in animals is constrained by both precursor availability and enzyme activity. Taken together, these findings support the conclusion that the endogenous synthesis of AAs limits growth, lactation, and reproduction in animals. This new knowledge can guide the optimization of human nutrition for improving health and well-being., (© 2016 American Society for Nutrition.)

Autophagy (i.e., "self-eating") and apoptosis (i.e., type I programmed cell death) are essential and intimately involved in molecular, cellular, and whole-body homeostasis in humans and animals. Autophagy has been categorized as a mechanism of intracellular degradation, recycling, defense, and survival. To date, three types of autophagy have been identified: macroautophagy, microautophagy, and chaperone-mediated autophagy. Recent discoveries strongly suggest that macroautophagy also modulates type II programmed cell death under specific circumstances. Autophagy and apoptosis are fundamentally distinct processes, but are interconnected by common stress initiators and intermediate regulators. During the past two decades, the role of amino acid metabolism and signaling in the regulation of apoptosis and autophagy has been intensively studied. In this review, we summarize recent advances in our understanding of the molecular mechanisms that regulate both autophagy and apoptosis in the context of amino acid signaling.

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., (© 2015 by the Society for Experimental Biology and Medicine.)

Recent studies indicate extensive catabolism of amino acids (AA) by the portal-drained viscera (PDV) of pigs and humans. Because of ethical concerns over invasive surgical procedures on infants or adults, in vivo investigations are often performed with the pig which is both an agriculturally important livestock species and a widely used animal model for nutritional and physiological studies in humans. Here, we described a new technique for implanting chronic catheters into the portal vein, ileal mesenteric vein, and carotid artery to study AA metabolism in the PDV of young pigs. This method allowed for the reduction of surgery time by 1 h and measurements of the entry of dietary AA into the portal circulation. Using such an approach, we found that dietary supplementation with 100 mg/kg chitosan (a prebiotic and a polysaccharide not digested by animal cells) reduced oxygen consumption, as well as the net absorption of dietary AA into the portal vein, thereby enhancing their bioavailability for extraintestinal tissues. In contrast, opposite results were obtained with dietary supplementation of 12% pea-hull (containing 95% of fermentable nonstarch polysaccharide). Thus, this improved technique is useful to quantify in vivo absorption and metabolism of dietary AA in young pigs.

Two experiments were conducted to evaluate the effects of dietary supplementation with Astragalus polysaccharide (APS) on growth performance, apparent ileal digestibilities (AID) of amino acids (AA), and their serum concentrations in early weaned piglets. In Exp. 1, 60 pigs were weaned at 21 days of age (BW 7.35 +/- 0.23 kg) and allocated to three treatments (20 pigs/treatment), representing supplementing 0.0% (control), 0.02% colistin (antibiotic), or 0.1% APS to a corn- and soybean meal-based diet. Average daily gain (ADG), average daily feed intake (ADFI), and feed/gain ratio (F/G) were measured weekly. Blood samples were obtained from five pigs selected randomly from each treatment for the measurement of serum free AA concentrations on days 7, 14, and 28. In Exp. 2, 12 pigs were weaned at 21 day of age (BW 7.64 +/- 0.71 kg), assigned to three treatment groups as in Exp. 1, and surgically fitted with a simple T-cannula at the terminal ileum. Ileal digesta samples were obtained for the measurement of AID of AA on days 7, 14 and 28. Dietary APS did not affect ADFI, but enhanced (P < 0.05) ADG by 11 and 4.4%, and improved F/G by 5.6 and 8.4%, respectively, compared with the control and antibiotic groups. Addition of APS to the diet increased AID and serum concentrations of most nutritionally essential and non-essential AA (including arginine, proline, glutamate, lysine, methionine, tryptophan, and threonine) on days 14 and 28. Circulating levels of total AA were affected by the age of pigs and treatment x time interaction. Collectively, these findings indicate that APS may ameliorate the digestive and absorptive function and regulate AA metabolism to beneficially increase the entry of dietary AA into the systemic circulation, which provide a mechanism to explain the growth-promoting effect of APS in early weaned piglets.

Arginine (Arg) has traditionally not been considered as a deficient nutrient in diets for gestating or lactating swine due to the assumption that these animals can synthesize sufficient amounts of Arg to meet their physiological needs. The lack of full knowledge about Arg nutrition has contributed to suboptimal efficiency of pork production. Over the past 25 yr, there has been growing interest in Arg metabolism in the pig, which is an agriculturally important species and a useful model for studying human biology. Arginine is a highly abundant amino acid in tissues of pigs, a major amino acid in allantoic fluid, and a key regulator of gene expression, cell signaling, and antioxidative reactions. Emerging evidence suggests that dietary supplementation with 0.5% to 1% Arg maintains gut health and prevents intestinal dysfunction in weanling piglets, while enhancing their growth performance and survival. Also, the inclusion of 1% Arg in diets is required to maximize skeletal muscle accretion and feed efficiency in growing pigs, whereas dietary supplementation with 1% Arg reduces muscle loss in endotoxin-challenged pigs. Furthermore, supplementing 0.83% Arg to cornand soybean meal-based diets promotes embryonic/fetal survival in swine and milk production by lactating sows. Thus, an adequate amount of dietary Arg as a quantitatively major nutrient is necessary to support maximum growth, lactation, and reproduction performance of swine. These results also have important implications for improving the nutrition and health of humans and other animals. [ABSTRACT FROM AUTHOR]

The intestine requires a high amount of energy to maintain its health and function; thus, energy deficits in intestinal mucosa may lead to intestinal damage. Asparagine (Asn) is a precursor for many other amino acids such as aspartate, glutamine and glutamate, which can be used to supply energy to enterocytes. In the present study, we hypothesise that dietary supplementation of Asn could alleviate bacterial lipopolysaccharide (LPS)-induced intestinal injury via improvement of intestinal energy status. A total of twenty-four weaned piglets were assigned to one of four treatments: (1) non-challenged control; (2) LPS+0 % Asn; (3) LPS+0·5 % Asn; (4) LPS+1·0 % Asn. On day 19, piglets were injected with LPS or saline. At 24 h post-injection, piglets were slaughtered and intestinal samples were collected. Asn supplementation improved intestinal morphology, indicated by higher villus height and villus height:crypt depth ratio, and lower crypt depth. Asn supplementation also increased the ratios of RNA:DNA and protein:DNA as well as disaccharidase activities in intestinal mucosa. In addition, Asn supplementation attenuated bacterial LPS-induced intestinal energy deficits, indicated by increased ATP and adenylate energy charge levels, and decreased AMP:ATP ratio. Moreover, Asn administration increased the activities of key enzymes involved in the tricarboxylic acid cycle, including citrate synthase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase complex. Finally, Asn administration decreased the mRNA abundance of intestinal AMP-activated protein kinase-α1 (AMPKα1), AMPKα2, silent information regulator 1 (SIRT1) and PPARγ coactivator-1α (PGC1α), and reduced intestinal AMPKα phosphorylation. Collectively, these results indicate that Asn supplementation alleviates bacterial LPS-induced intestinal injury by modulating the AMPK signalling pathway and improving energy status. [ABSTRACT FROM PUBLISHER]

Pro-inflammatory cytokines play a key role in many models of hepatic damage. In addition, asparagine (Asn) plays an important role in immune function. We aimed to investigate whether Asn could attenuate lipopolysaccharide (LPS)-induced liver damage. Forty-eight castrated barrows were allotted to four groups including: (1) non-challenged control; (2) LPS-challenged control; (3) LPS+0·5 % Asn; and (4) LPS+1·0 % Asn. After 19 d feeding with control, 0·5 or 1·0 % Asn diets, pigs were injected with LPS or saline. Blood and liver samples were obtained at 4 h (early stage) and 24 h (late stage) post-injection. Asn alleviated liver injury, indicated by reduced serum aspartate aminotransferase and alkaline phosphatase activities linearly and quadratically; it increased claudin-1 protein expression linearly and quadratically at 24 h, and less severe liver morphological impairment at 4 or 24 h. In addition, Asn decreased mRNA expression of TNF-α and heat shock protein 70 (HSP70) linearly and quadratically at 4 h; it increased TNF-α mRNA expression, and HSP70 protein expression linearly and quadratically at 24 h. Moreover, Asn increased inducible NO synthase activity linearly and quadratically. Finally, Asn down-regulated the mRNA expression of Toll-like receptor 4 (TLR4) signalling molecules (TLR4, IL-1 receptor-associated kinase 1 (IRAK1), TNF-α receptor-associated factor 6), nucleotide-binding oligomerisation domain protein (NOD) signalling molecules (NOD1, NOD2 and their adaptor molecule receptor-interacting serine/threonine-protein kinase 2 (RIPK2)), and NF-κB p65 linearly or quadratically at 4 h. Oppositely, Asn up-regulated mRNA expressions of TLR4 and NOD signalling molecules (TLR4, myeloid differentiation factor 88, IRAK1, NOD2 and RIPK2), and their negative regulators (radioprotective 105, single Ig IL-1R-related molecule, Erbb2 interacting protein and centaurin β1) linearly or quadratically at 24 h. These results indicate that, in early and late stages of LPS challenge, Asn improves liver integrity and exerts different regulatory effects on mRNA expression of TLR4 and NOD signalling molecules. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to investigate whether aspartate (Asp) could improve liver energy status in the lipopolysaccharide (LPS)-challenged pigs. Methods: Twenty-four weaned pigs were assigned to four treatments: (1) nonchallenged control (control diet and saline-treated); (2) LPS-challenged control (the same control diet and LPS-challenged); (3) LPS + 0.5 % Asp treatment (0.5 % Asp diet and LPS-challenged); and (4) LPS + 1.0 % Asp treatment (a 1.0 % Asp diet and LPS-challenged). On d 19, the pigs were injected intraperitoneally with Escherichia coli LPS at 100 μg/kg body weight, and the same volume of 0.9 % NaCl solution, respectively. All pigs were slaughtered at 24 h after LPS or saline injection, and the liver was collected for further analysis. Results: Dietary supplementation with Asp improved liver energy status evidenced by the increased ATP concentration and adenylate energy charges, and the decreased AMP concentration and AMP/ATP ratio ( p < 0.05). Asp supplementation increased the mRNA expression of key enzymes in hepatic glycolysis and tricarboxylic acid (TCA) cycle, including pyruvate kinase and citrate synthase ( p < 0.05), and had a tendency to increase hepatic pyruvate dehydrogenase and isocitrate dehydrogenase β mRNA expression ( p < 0.10). In addition, Asp increased the mRNA expressions of hepatic AMP-activated protein kinase (AMPK) α1, AMPKα2, silent information regulator (Sirt1), and proliferator-activated receptor-γ coactivator 1α (PGC1α) ( p < 0.05). Moreover, Asp increased AMPKα phosphorylation ( p < 0.05). Conclusions: These results indicated that dietary supplementation of Asp could improve energy status in LPS-injured liver, which might result from motivating the metabolism pathway of TCA cycle and glycolysis and stimulating the AMPK signaling pathway. [ABSTRACT FROM AUTHOR]