The Glutamine/Glutamate Couplet and Cellular Function

Abstract

All cells require glutamine as a nitrogen donor as well as an energy source for cell-specific functions. Understanding how glutamine utilization is metered to these demands is fundamental to basic cell processes as well as to therapeutic manipulation of regulatory mechanisms. The regulatory role of the glutamine/glutamate couplet in cellular function is illustrated for acid-base homeostasis and for production of the extracellular matrix.

Serum Concentration of Free Amino Acids in Dogs Suffering From Perianal Tumours

“…Thus, the observed significant increase in serum concentrations of all amino acids in dogs possessing neoplastic changes may be connected with enhanced transport and metabolic processes. Additionally, it should be noted that the observed reduced serum concentration of glutamine in dogs with perianal tumours is associated with higher glutamic acid level, since glutamine may be easily converted into glutamic acid (32). The decreased serum glutamine concentration in tumour-affected dogs may also result from its reduced amount in the intracellular and extracellular compartments at hypercatabolic pathological state, such as neoplastic disease (34).…”

Reduction of Proteinuria through Podocyte Alkalinization

“…1B). Glutamine is involved in a wide variety of metabolic pathways and plays key roles in many physiological processes in various organs (38,39). Glutamine is the most abundant plasma amino acid (40,41), as well as the most plentiful amino acid, in routine podocyte culture medium used for cell culture.…”

Role of Glutamate Dehydrogenase in Cancer Growth and Homeostasis

“…Glutaminolysis as illustrated in Figure 2 is associated with the increased expression of both the extrinsic cell membrane phosphate independent glutaminase/gamma glutamyltransferase/gamma glutamyltranspeptidase (PIG, GGT, GGTP) which generates extracellular glutamate [2,12] and intracellular phosphate dependent glutaminases, Phosphate dependent glutaminases (PDG,GLS1 and GAC, [13,14]) which generates glutamate cytosolically [2,13]; extracellular glutamate can be transported(GLAST, Figure2) into the cytosol functioning as an inhibitor of the intracellular glutaminases [2]. Noteworthy, c-myc signaling up-regulates both the cell membrane glutamine transporter (ASC, Figure 2) and the intracellular glutaminases in cancer cells [15].…”

“…pyruvate in the process of generating alpha ketoglutarate). Under physiological conditions plasma glutamate concentration, 10-20uM, is limiting for GDH flux supplying TCA intermediates while plasma glutamine concentration, 600uM, is not [2]. The conversion of 15N amide labeled glutamine to 15N ammonium (Figure1, Rxn1) approximates the net glutaminase flux generating glutamate and ammonium, both potential substrates for GDH.…”

“…[1] Deamidation coupled to GDH deamination yielding 2NH4+/Gln and net keto acid (αKG). [2] Deamination coupled to ALT-mediated transamination yielding 1 NH4+/Gln and no net acid production. [3] Deamidation coupled to GDH reductive amination and transamination yielding < 1 NH4+/Gln and net keto acid…”