Glutamine metabolism

For Further Reading J. A. Kraut and N. E. Madias, Approach to patients with acid—base disorders, Respiratory Care, vol. 46, no. 4, April 2001, pp. 392—403. J. Squires, Artificial blood, Science, vol. 295, Feb. 8, 2002, pp. 1002-1005. Lynn Taylor and Norman P. Curthoys, Glutamine metabolism Role in Acid-Base Balance, Biochemistry and Molecular Biology Education, vol. 32, no. 5, 2004, pp. 291-304. 

Curthoys NP, Watford M Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr 1995 15 133. 

GLUTAMATE/GLUTAMINE METABOLISM IS LINKED TO ENERGY METABOLISM 547... 

Glutamate and glutamine metabolism is compartmentalized in brain 548 A specialized glutamate-glutamine cycle operates in GABAergic neurons and surrounding astrocytes 549 Several shuttles act to transfer nitrogen in brain 549... 

Schousboe, A., Westergaard, N., Sonnewald, U. etal. Glutamate and glutamine metabolism and compartmenta-tion in astrocytes. Dev. Neurosci. 15 359-366,1993. 

Figure 8.27 Pathway of glutamine metabolism in the intestinal cells. Glutamine is metabolised to alanine to generate ATP alanine is released into the blood to be taken up by the liver.

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

Comparison of the early stages of glutamine metabolism in kidney, intestine and lymphocytes... 

Although glutamine metabolism in these various tissues is important in the generation of ATP, the metabolism is different due to other functions of glutamine metabolism... 

Figure 8.30 Different roles of periportal and perivenous cells in the liver in respect of glutamine metabolism. Glutamine is converted to glucose in periportal cells via gluconeogenesis in perivenous cells, ammonia is taken up, to form glutamine, which is released into the blood. This emphasises the importance of the liver in removing ammonia from the blood, i.e. if possesses two process to ensure that all the ammonia is removed.

Tin metabolic acidosis (p. 652) there is an increase in glutamine processing by the kidneys. Not all the excess NH4 thus produced is released into the bloodstream or converted to urea some is excreted directly into the urine. In the kidney, the NH% forms salts with metabolic acids, facilitating their removal in the urine. Bicarbonate produced by the decarboxylation of a-lcetoglutarate in the citric acid cycle can also serve as a buffer in blood plasma. Taken together, these effects of glutamine metabolism in the kidney tend to counteract acidosis. ... 

The glutamine synthetase of E. coli is independently modulated by various products of glutamine metabolism (see Fig. 22-6). In this concerted inhibition, the extent of enzyme inhibition is greater than the sum of the separate inhibitions caused by each product. For E. coli grown in a medium rich in histidine, what would be the advantage of concerted inhibition ... 

It should be noted that there is a growing list of conditionally essential amino acids. These are amino acids that must be augmented through the diet under a variety of special circumstances. Often these circumstances include infancy (where the various enzyme systems for metabolism have not been fully expressed) or periods of metabolic stress due to injury or illness. Conditionally essential amino acids include taurine (infants) and glutamine (metabolic stress). 

K Herskowitz, WW Souba. Intestinal glutamine metabolism during critical illness a surgical perspective. Nutrition 6 199-206, 1990. 

Alanine, an end product of glutamine metabolism in many mammalian cells (McKeenhan, 1986), is also formed by Sf9 cells. In a normal batch... 

There may be several mechanisms for these metabolic effects. Unsaturated fatty acids have been shown to directly activate specific enzymes and to induce DNA synthesis and cytokine release from lymphocytes (Karsten et al., 1994). The induction of specific protein synthesis may produce the reduction in glutamine metabolism. The increase in the robustness of the fatty acid-grown hybridomas in agitated cultures could be explained by a high incorporation of the available fatty acids into the cellular phospholipids fraction, which is a major structural component of the outer membrane of the cell (Butler et al., 1999). 

As previously stated, ammonium in cell culture medium is the product of glutamine metabolism and its spontaneous decomposition at 37°C. Negrotti et al. (1989) showed that the half-life for glutamine at 37°C and pH 7.2 is only 7 days. The effects of ammonium on cell metabolism are observed from concentrations as low as 2 mM, which is easily reached in culture systems (Table 4.2). For example, the spontaneous decomposition of glutamine can result in 0.1 mM ammonia per day (Butler and Spier, 1984). Anchorage-dependent cells grown on microcarriers produce between 2 and 3 mM ammonia after growth in a batch culture (Butler et al.,... 

Effects of ammonium on mammalian cell cultures. (A) Effects of ammonium generated by glutamine metabolism. (B) Effects of ammonium generated by glutamine decomposition or by ammonium addition in the culture medium. 

EXTRACELLULAR SPACE (glutamine decomposition) OR MITOCHONDRIA (glutamine metabolism)... 

Bell SL, Bushell ME, Scott MF, Warded JN, Spier RE, Sanders PG (1992), Genetic modification of hybridoma glutamine metabolism physiological consequences. In Proceedings of the 11th ESACT Meeting, Brighton, UK, pp. 180-182. 

Bell SL, Bebbington C, Scott MF, Wardell JN, Spier RE, Bushel ME, Sanders PG (1995), Genetic engineering of hybridoma glutamine metabolism, Enzyme Microb. Technol. 17 98-106. 

Fitzpatrick L, Jenkins HA, Butler M (1993), Glucose and glutamine metabolism of a murine B-lymphocyte grown in batch culture, Appl. Biochem. Biotechnol. 43 93-116. 

Neerman J, Wagner R (1996), Comparative analysis of glucose and glutamine metabolism in transformed mammalian cell lines, insect and primary liver cells, J. Cell. Physiol. 166 152-169. 

Paredes C, Prats E, Cairo JJ, Azorin F, Cornudella L, Godia F (1999), Modification of glucose and glutamine metabolism in hybridoma cells through metabolic engineering, Cytotechnology 30 85-93. 

Sri-Pathmanathan, R.M., Braddock, P., Brindle, K.M. (1989). 31P NMR studies of glucose and glutamine metabolism in cultured mammalian cells. Biochim. Biophys. Acta 1051, 131-137. 

Newsholme, E.A., Crabtree, B., Ardawi, S.M. (1985). Glutamine metabolism in lymphocytes Its biochemical, physiological and clinical importance. Quart. J. Exp. Physiol. 70, 473-489. 

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