Glutamine, gene expression, and cell function

Abstract

Glutamine is the most abundant free amino acid in the body and is known to play a regulatory role at the gene and protein level in several cell specific processes including metabolism (e.g. oxidative fuel, gluconeogenic precursor and lipogenic precursor), cell integrity (survival, cell proliferation), protein synthesis and degradation, redox potential, respiratory burst, insulin resistance, insulin secretion and extracellular matrix synthesis. Glutamine has been shown to regulate the expression of many genes related to metabolism, signal transduction, cell defense and repair and to activate intracellular signaling pathways. Thus, the function of glutamine goes beyond that of a simple metabolic fuel or protein precursor as previously assumed. In this review, we have attempted to identify some of the common mechanisms underlying glutamine dependent changes in gene and protein expression and cellular function.

Brain glutaminases

“…Therefore, we cannot exclude that GIP could be involved in the targeting of L-type GA to neuronal nuclei. A potential nuclear function for GA could be the regulation of Gln/Glu levels (27), taking into account that Gln is a signal molecule involved in gene expression (73,74). Therefore, the significance of its nuclear localization could be as simple as being an enzyme controlling in situ the Gln levels in the nucleoplasm and thus being indirectly involved in the expression of Gln-regulated genes (Figure 2).…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Glutamine also influences the expression of a number of genes related to cell protection and survival [215]. Importantly, glutamine is the immediate precursor of the glutamate moiety for glutathione (GSH = γ-glutamyl-cysteinylglycine), the main soluble antioxidant species within the cell, this being demonstrated in a number of cell types and tissues [208,[212][213][214][215][216][217][218][219]. Inasmuch as redox imbalances are characteristic of degenerative disorders [140,148] and aggregative diseases [141-143, 153, 154], glutamine status becomes of importance in dictating a healthy condition.…”

“…Several studies with different cell types, including muscle, intestinal mucosa, immune cells, specific neurons of the central nervous system, hepatocytes, and pancreatic β cells, just to cite a few examples, have irrefragably demonstrated that glutamine is required in incubation/culture media for normal growth and function [214,216,218,288]. In catabolic (e.g., sepsis, recovery from burns and surgery, exhaustive exercise) and inflammation-related (age-associated chronic diseases) situations, glutamine requirements increase dramatically.…”

Immunonutrition: a South African perspective

“…50 It may also serve as a vital cellsignalling molecule in states of illness and injury. 52 In this regard, glutamine has been shown to regulate the expression of many genes that relate to metabolism, cell repair and defense, signal transduction and activation of intracellular signalling pathways. 52 Glutamine release could further serve as a "stress signal" to the organism to turn on genes that are vital to cellular protection and immune regulation.…”

“…52 In this regard, glutamine has been shown to regulate the expression of many genes that relate to metabolism, cell repair and defense, signal transduction and activation of intracellular signalling pathways. 52 Glutamine release could further serve as a "stress signal" to the organism to turn on genes that are vital to cellular protection and immune regulation. 50 An example of the latter is glutamine's potential key role in enhancing the synthesis of heat-shock proteins (HSPs), which are essential to cellular recovery following injury, and for protection against organ failure.…”