Glutamine metabolism and its physiologic importance.

The amino acid glutamine has important and unique metabolic functions. It is the most abundant free amino acid in the circulation and in intracellular pools and a precursor for the synthesis of amino acids, proteins, nucleotides, and many other biologically important molecules. It is the most important precursor for ammoniagenesis in the kidney, the major end product of ammonia-trapping pathways in the liver, a substrate for gluconeogenesis, and an oxidative fuel in rapidly proliferating cells and tissues. Glutamine also may have a number of important regulatory roles, increasing protein synthesis and decreasing protein degradation in skeletal muscle and stimulating glycogen synthesis in the liver. The demonstration that glutamine concentrations decrease and tissue glutamine metabolism increases markedly in many catabolic, stressful disease states has led to a reconsideration of the classification of glutamine as a nonessential amino acid and to the alternative hypothesis that glutamine may be a conditionally essential nutrient. This hypothesis has been supported by recent studies that have shown trophic effects of glutamine-supplemented diets on the growth of specific tissues and on total body nitrogen balance. These observations form the basis for current efforts to define the clinical usefulness of glutamine-supplemented nutrition.