Glutamine, brain

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

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. 

Glucosidase and 0-galactosidase (sweet almond emulsin)[36] Glutamine synthetase (native octameric brain) 371 Glycogen phosphorylase At3 ]... 

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. 

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... 

One result of the selective localization of brain enzymes is that astrocytes must provide certain substrates (e.g. glutamine) to neurons for replenishment of the neuronal TCA cycle and for neurotransmitter synthesis [58]. Thus, astrocytes and neurons are essential partners in brain function. See also discussion in Chapter 15. 

Martinez-Hernandez, A., Bell, K. P. and Norenberg, M. D. Glutamine synthetase glial localization in rat brain. Science 195 1356-1358,1977. 

Berl, S., Nicklas, W. J. and Clarke, D. D. Compartmentation of citric acid cycle metabolism in brain labelling of glutamate, glutamine, aspartate and gaba by several radioactive tracer metabolites. J. Neurochem. 17 1009-1015, 1970. 

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