Glutamine oxidation

There are also three phases in the pathway of glutamine oxidation ... 

Figure 9.4 Reactions of glutaminolysis the pathway for glutamine oxidation. Reaction 1 is catalysed by glutaminase, reaction 2 by glutamate aminotransferase, and reaction 8 by aspartate aminotransferase all other enzymes are those of the Krebs cycle (3-7). (See also Chapter 8).

The involvement of isobutylhydroxylamine, (CH3)2CHCH2NH—OH (4), and of HA (NH2OH) in the biosynthesis of the antibiotics valanimycin (5) and nebularine (6), respectively, has been demonstrated in Streptomyces species (see Section n.B). In the case of nebularine, HA is released in the final step of its production by enzymatically induced deamination of adenosine, while the isobutylhydroxylamine is a precursor for the biosynthesis of valanimycin. In cyanobacterium, the presence of free and bound HA was demonstrated to be a product of enzyme-mediated glutamine oxidation ... 

Lee, W.N., J. Edmond, S. Bassilian and J. W. Morrow, 1996. Mass isotopomer study of glutamine oxidation and synthesis in primary culture of astrocites. Dev. Neurosci.18,469-477. 

Oliver, C.N., Starke-Reed, P.E., Stadtman, E.R., Liu, G.J., Carney, J.M. and Floyd, R.A. (1990). Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc. Natl Acad. Sd. USA 87, 5144-5147. 

In earlier studies the in vitro transition metal-catalyzed oxidation of proteins and the interaction of proteins with free radicals have been studied. In 1983, Levine [1] showed that the oxidative inactivation of enzymes and the oxidative modification of proteins resulted in the formation of protein carbonyl derivatives. These derivatives easily react with dinitrophenyl-hydrazine (DNPH) to form protein hydrazones, which were used for the detection of protein carbonyl content. Using this method and spin-trapping with PBN, it has been demonstrated [2,3] that protein oxidation and inactivation of glutamine synthetase (a key enzyme in the regulation of amino acid metabolism and the brain L-glutamate and y-aminobutyric acid levels) were sharply enhanced during ischemia- and reperfusion-induced injury in gerbil brain. 

Cervera and Levine [81] studied the mechanism of oxidative modification of glutamine synthetase from Escherichia coli. It was found that active oxygen species initially caused inactivation of the enzyme and generated a more hydrophilic protein, which still was not a substrate for the protease. Continuous action of oxygen species resulted in the formation of oxidized protein subjected to the proteolytic attack of protease. 

Glutamine synthetase, a brain Mn enzyme, is located mainly in astrocytes, and its synthesis may be modulated by nitric oxide (496). Inhibition of this enzyme could be relevant to aging diseases (497). There is evidence that human NT2-N neurons die via ionotropic glutamate receptor-mediated mechanisms when exposed to hypoxia in the presence of glutamate (498). 

Additionally, several amino acids may undergo transamination to produce glutamate which in the liver is oxidatively deaminated to form 2-oxoglutarate (2-OG, see Figure 6.6), a substrate of the TCA cycle. Alternatively, glutamate maybe converted into glutamine, an important but often overlooked fuel substrate. 

The 2-oxoglutarate produced is recycled for transamination or may enter the TCA cycle. The ammonia liberated by oxidative deamination is used to form glutamine (from glutamate, catalysed by glutamine synthase) prior to export from the muscle cell ... 

The two important fuels for colonocytes are glutamine and short-chain fatty acids. The oxidation of both fuels provides ATP for the cells, which is important not only to maintain digestive and absorptive functions but also to maintain membrane structure and hence the physical barrier between the lumen and the blood and peritoneal cavity. This barrier normally prevents significant rates of translocation of bacteria into the peritoneal cavity and thence into the blood. If this barrier is breached, translocation of pathogens and... 

Figure 8.23 Formation of glutamine from glucose and branched-chain amino adds in muscle and adipose tissue and probably in the lung. Oxoacids may also be released into blood for oxidation in the liver.

From the above discussion, it is clear that some tissues synthesise and then release glutamine into the blood and others take up glutamine and use it as a fuel and/or as a nitrogen donor. Hence, glutamine can be considered as a fuel in the blood, alongside glucose and fatty acids. Its oxidation in the Krebs cycle is described in Chapter 9. The... 

It has been considered that glucose and fatty acids (long or short chain) are the major fuels for oxidation in most cells, but the amino acid glutamine is now known to be a major fuel for some cells (Table 9.1). 

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