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because it contains two nitrogen moieties. It is important in the generation of purines and pyrimidines necessary for DNA biosynthesis (Martin, 1985) and serves as a precursor in some tissues for metabolically generated bases (Welbourne, 1995) (that is, endogenously synthesized purines and pyrimidines; those not from dietary sources) and glycoproteins. Glutamine is also a regulator (or co-regulator) of cell proliferation (Kandil et al., 1995), the generation of heat-shock proteins2 (Ehrenfried et al., 1995), and the expression of certain cell surface receptors (Spittler et al., 1995). It is not known if some of these specific activities involve direct or indirect genetic regulatory mechanisms.

Glutamine may also be rate limiting for the synthesis of glutathione, one of the most important intracellular antioxidants. Studies show that in the presence of cysteine, the provision of glutamine will enhance glutathione stores and reduce oxidant damage (Hong et al., 1992).

This chapter reviews the pertinent clinical studies that suggest an association between glutamine and the immune defenses of the body.

Physiologic Biochemistry

Although almost all tissues contain the enzymes for glutamine synthesis, most glutamine is synthesized in skeletal muscle and brain, and these are the major organs that export glutamine. Liver, however, has the capacity to both consume and produce glutamine, depending on a variety of controlling factors. Because of the large mass of skeletal muscle, most glutamine comes from this tissue and is exported via the bloodstream to visceral organs (Souba et al., 1985). Under normal conditions, glutamine is maintained in high concentrations within the skeletal muscle free amino acid pool. Excluding taurine, glutamine represents about 60 percent of the free amino acids in skeletal muscle and maintains an intracellular concentration of about 20 mmol/Liter intracellular water. With normal plasma concentrations ranging from 600 to 650 µmol/Liter, this large concentration gradient (about 30:1) favors rapid transfer of a large quantity of glutamine from this intracellular store into the bloodstream (Muhlbacher et al., 1984). Because skeletal muscle intracellular glutamine concentrations fall with starvation and the stress of illness, muscle biopsy followed by analysis of intracellular glutamine concentration has been used as a marker of nutritional status in depleted patients and may even be predictive of a fatal outcome (Roth et al., 1982). Other studies have demonstrated that the skeletal muscle intracellular concentration of glutamine is related to the rate of protein synthesis in skeletal muscle (Jepson et al., 1988; MacLennan et al., 1987). Finally, the exogenous administration (supplementation) of glutamine (by addition to total parenteral nutrition [TPN]) attenuates the usual fall in

2  

Heat-shock proteins are a class of proteins whose synthesis is stimulated by thermal temperatures (greater than normal growth temperatures) and other stressors. These proteins are believed to play an essential role in adaptation and protection of cells from damage.



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