l-Glutamate nutrition and metabolism in swine

Amino acids (AA) have enormous physiological importance, serving as building blocks for proteins and substrates for synthesis of low-molecular-weight substances. Based on growth or nitrogen balance, AA were traditionally classified as nutritionally essential or nonessential for animals. Although those AA that are not synthesized in eukaryotes (nutritionally essential AA, EAA) must be present in animal diets, nutritionally nonessential AA (NEAA) have long been ignored for all species. Emerging evidence shows that nonruminants cannot adequately synthesize NEAA or conditionally essential AA (CEAA) to realize their growth or anti-infection potential. Likewise, all preformed AA are needed for high-producing cows and rapidly growing ruminants. Many NEAA and CEAA (e.g., arginine, glutamine, glutamate, glycine, and proline) and certain EAA (e.g., leucine and tryptophan) participate in cell signaling, gene expression, and metabolic regulation. Thus, functions of AA beyond protein synthesis must be considered in dietary formulations to improve efficiency of nutrient use, growth, development, reproduction, lactation, and well-being in animals.

Glutamine is synthesized primarily in skeletal muscle, lungs, and adipose tissue. Plasma glutamine plays an important role as a carrier of nitrogen, carbon, and energy between organs and is used for hepatic urea synthesis, for renal ammoniagenesis, for gluconeogenesis in both liver and kidney, and as a major respiratory fuel for many cells. The catabolism of glutamine is initiated by either of two isoforms of the mitochondrial glutaminase. Liver-type glutaminase is expressed only in periportal hepatocytes of the postnatal liver, where it effectively couples ammonia production with urea synthesis. Kidney-type glutaminase is abundant in kidney, brain, intestine, fetal liver, lymphocytes, and transformed cells, where the resulting ammonia is released without further metabolism. The two isoenzymes have different structural and kinetic properties that contribute to their function and short-term regulation. Although there is a high degree of identity in amino acid sequences, the two glutaminases are the products of different but related genes. The two isoenzymes are also subject to long-term regulation. Hepatic glutaminase is increased during starvation, diabetes, and feeding a high-protein diet, whereas kidney-type glutaminase is increased only in kidney in response to metabolic acidosis. The adaptations in hepatic glutaminase are mediated by changes in the rate of transcription, whereas kidney-type glutaminase is regulated at a posttranscriptional level.

l-Glutamate is one of the most abundant amino acids in alimentary proteins, but its concentration in blood is among the lowest. This is largely because l-glutamate is extensively oxidized in small intestine epithelial cells during its transcellular journey from the lumen to the bloodstream and after its uptake from the bloodstream. This oxidative capacity coincides with a high energy demand of the epithelium, which is in rapid renewal and responsible for the nutrient absorption process. l-Glutamate is a precursor for glutathione and N-acetylglutamate in enterocytes. Glutathione is involved in the enterocyte redox state and in the detoxication process. N-acetylglutamate is an activator of carbamoylphosphate synthetase 1, which is implicated in l-citrulline production by enterocytes. Furthermore, l-glutamate is a precursor in enterocytes for several other amino acids, including l-alanine, l-aspartate, l-ornithine, and l-proline. Thus, l-glutamate can serve both locally inside enterocytes and through the production of other amino acids in an interorgan metabolic perspective. Intestinal epithelial cell capacity to oxidize l-glutamine and l-glutamate is already high in piglets at birth and during the suckling period. In colonocytes, l-glutamate also serves as a fuel but is provided from the bloodstream. Alimentary and endogenous proteins that escape digestion enter the large intestine and are broken down by colonic bacterial flora, which then release l-glutamate into the lumen. l-Glutamate can then serve in the colon lumen as a precursor for butyrate and acetate in bacteria. l-Glutamate, in addition to fiber and digestion-resistant starch, can thus serve as a luminally derived fuel precursor for colonocytes.