Functional amino acids in growth, reproduction, and health

Abstract

Amino acids (AA) were traditionally classified as nutritionally essential or nonessential for animals and humans based on nitrogen balance or growth. A key element of this classification is that all nonessential AA (NEAA) were assumed to be synthesized adequately in the body as substrates to meet the needs for protein synthesis. Unfortunately, regulatory roles for AA in nutrition and metabolism have long been ignored. Such conceptual limitations were not recognized until recent seminal findings that dietary glutamine is necessary for intestinal mucosal integrity and dietary arginine is required for maximum neonatal growth and embryonic survival. Some of the traditionally classified NEAA (e.g. glutamine, glutamate, and arginine) play important roles in regulating gene expression, cell signaling, antioxidative responses, and immunity. Additionally, glutamate, glutamine, and aspartate are major metabolic fuels for the small intestine and they, along with glycine, regulate neurological function. Among essential AA (EAA), much emphasis has been placed on leucine (which activates mammalian target of rapamycin to stimulate protein synthesis and inhibit proteolysis) and tryptophan (which modulates neurological and immunological functions through multiple metabolites, including serotonin and melatonin). A growing body of literature leads to a new concept of functional AA, which are defined as those AA that regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of organisms. Both NEAA and EAA should be considered in the classic "ideal protein" concept or formulation of balanced diets to maximize protein accretion and optimize health in animals and humans.

Figure 1

Roles of AA in nutrition and whole-body homeostasis. Besides serving as building blocks for proteins, AA have multiple regulatory functions in cells. These nutrients are crucial for growth, development, and health of animals and humans.

Figure 2

Catabolism of nutritionally EAA for the synthesis of AA in animals. Dietary intake of most EAA exceeds their use for protein synthesis in the body. In contrast, the typical corn- and soybean meal-based diet cannot provide sufficient amounts of arginine, aspartate, glutamate, glutamine, glycine, and proline for protein accretion for young pigs, and these AA must be synthesized from EAA. BCAA, branched-chain AA; D3PG, D-3-phosphoglycerate; Gluc, glucose; HYP, hydroxyproline; TF, tetrahydrofolate.

Figure 3

Models for regulatory roles of AA in protein synthesis. Provision of sufficient amounts of AA promotes the binding of GTP to Rag GTPase leading to mTORC1 activation, while reducing concentrations of uncharged tRNA and activity of the GCN2-independent eIF2B kinase leading to increased activity of eIF2B. All of these changes stimulate the initiation of protein synthesis in cells. Abbreviations: eIF2α, eukaryotic translation initiation factor 2α; eIF2B, eukaryotic translation initiation factor 2B; GCN2, general control nonderepressible protein 2; mTORC1, mammalian target of rapamycin complex 1; S6K1, ribosomal protein S6 kinase-1; 4EBP1, eIF4E-binding protein-1. ↑, increase in concentration or activity; ↓, decrease in concentration or activity.