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Primary Functions of Glutamine in Cell Culture Systems:

Glutamine supports the growth of cells that have high energy demands and synthesize large amounts of proteins and nucleic acids. It is an alternative energy source for rapidly dividing cells and cells that use glucose inefficiently. Cells require nitrogen atoms to build molecules such as nucleotides, amino acids, amino-sugars and vitamins. Ammonium is an inorganic source of nitrogen that exists primarily as a positively charged cation, NH4+, at physiological pH. Ammonium nitrogen used by cells is initially incorporated into organic nitrogen as an amine of glutamate or an amide of glutamine. These two amino acids provide the primary reservoirs of nitrogen for the synthesis of proteins, nucleic acids and other nitrogenous compounds. Reactions that fix nitrogen into glutamate and glutamine consume energy equivalents. Glutamate is synthesized from ammonium and alpha ketoglutaric acid, a tricarboxylic acid (TCA) cycle intermediate. Its synthesis requires the oxidation of either NADH or NADPH. Glutamine is formed from ammonium and glutamate and its synthesis consumes ATP. The enzymes involved in glutamate synthesis, glutamate dehydrogenase (EC 1.4.1.4) and glutamate synthase (EC 1.4.1.13) are reversible. The enzyme responsible for glutamine synthesis, glutamine synthetase (EC 6.3.1.2), is highly regulated to limit the production of glutamine to cell requirements. The catabolism of glutamine to glutamate and ammonium is mediated by mitochodrial enzymes called glutaminases (EC 3.5.1.2 ). Ammonium produced in vivo can be metabolized to urea. In vitro, ammonium is not metabolized to urea. Under some in vitro conditions, ammonia accumulates in the extracellular medium as ammonium ion. Roles of glutamine: * Glutamine contains one atom of nitrogen as an amide and another atom of nitrogen as an amine and it transports and delivers nitrogen to cells in quantities that are toxic as free ammonium. * Glutamine amide nitrogen is used in the synthesis of the vitamins NAD and NADP, purine nucleotides, CTP from UTP and asparagine. Nitrogen initially stored in glutamine can also be used to produce carbamyl phosphate for the synthesis of pyrimidines. * Glutamine is a precursor of glutamate, a key amino acid used for the transamination of alpha ketoacids to form other alpha amino acids. * When glucose levels are low and energy demands are high, cells can metabolize amino acids for energy. Glutamine is one of the most readily available amino acids for use as an energy source and it is a major source of energy for many rapidly dividing cell types in vitro.

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Q: What is the role of glutamine in cell culture?
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