Glutamine synthetase regulation

McDermott RH, Butler M (1993), Uptake of glutamate, not glutamine synthetase, regulates adaptation of mammalian cells to glutamine-free medium, J. Cell Sci. 104 51-58. 

ER Stadtman (2001) The Story of Glutamine Synthetase Regulation, J Biol Chem 276(48) 44357 14364... 

Uridylylation UTP UMP PPi Tyr Pn protein (another form of glutamine synthetase regulation)... 

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. 

Covalent interconversion of enzymes is well established as a fundamental theme in metabolic regulation. The prototypic reversible interconverting systems include the sequence of phosphorylation/dephosphorylation steps in the activation of mammalian glycogen phosphorylase and pyruvate dehydrogenase as well as the nucleotidyla-tion/denucleotidylation using UTP and ATP in the bacterial glutamine synthetase cascade (see Fig. 1.). 

M FIGURE 22-7 Second level of regulation of glutamine synthetase covalent modifications, (a) An adenylylated Tyr residue, (b) Cascade leading to adenylylation (inactivation) of glutamine synthetase. AT represents adenylyltransferase UT, uridylyltransferase. Details of this cascade are discussed in the text. 

Allosteric regulation can be considerably more complex. An example is the remarkable set of allosteric controls exerted on glutamine synthetase of E. coli (Fig. 22-6). Six products derived from glutamine serve as negative feedback modulators of the enzyme, and the overall effects of these and other modulators are more than additive. Such regulation is called concerted inhibition. 

Elaborate cascades initiate the clotting of blood (Chapter 12) and the action of the protective complement system (Chapter 31). Cascades considered later in the book are involved in controlling transcription (Fig. 11-13) and in the regulation of mammalian pyruvate dehydrogenase (Eq. 17-9), 3-hydroxy-3-methyl-glutaryl-CoA reductase and eicosanoids (Chapter 21), and glutamine synthetase (Chapter 24). 

Cock, J.M., Brock, I.W., Watson, A.T., Swarup, R., Morby, A.P. Cullimore, J.V. (1991). Regulation of glutamine synthetase genes in leaves of Phaseolus vulgaris. Plant Molecular Biology 17, 761-71. 

Edwards, J.W. Coruzzi, G.M. (1989). Light and photorespiration act in concert to regulate the expression of the nuclear gene for chloroplast glutamine synthetase. The Plant Cell 1, 241-8. 

Glutamine synthetase genes are regulated by ammonia provided externally or by symbiotic nitrogen fixation. The EMBO Journal 6, 1167-71. 

Miao, G.-H., Hirel, B., Marsolier, M.C., Ridge, R.W. Verma, D.P.S. (1991). Ammonia-regulated expression of a soybean gene encoding glutamine synthetase in transgenic Lotus corniculatus and tobacco. The Plant Cell 3, 11-22. 

Hirel, B., Bouet, C., King, B., Layzell, D., Jacobs, F. Verma, D.P.S. (1987). Glutamine synthetase genes are regulated by ammonia provided externally or by symbiotic nitrogen fixation. The EM BO Journal 5, 1167-71. 

El Alaoui, S., Diez, J., Humanes, L., Toribio, F., Partensky, F., and Garcia-Fernandez, J. M. (2001). In vivo regulation of glutamine synthetase activity in the marine chlorophyU b-containing cyanobacterium Prochlorococcus sp strain PCC 9511 (oxyphotobacteria). Appl. Environ. Microbiol. 67, 2202-2207. 

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