Brain glutamate

Glutamate is a small amino acid which constitutes the most important neurotransmitter at excitatory synapses in the mammalian brain. Glutamate can act on several different types of receptors including cation channels and G-protein-coupled receptors. 

Hsu, CC, Thomas, C, Chen, W, Davis, KM, Foos, T, Chen, JL, Wu, E, Floor, E, Schloss, JV and Wu, JY (1999) Role of synaptic vesicle proton gradient and protein phosphorylation on ATP-mediated activation of membrane-associated brain glutamate decarboxylase. J. Biol. Chem. 274 24366-24371. 

An overview of some of the processes involved in synaptic transmission is shown in Figure 10-1. Many of the processes are discussed below or in other chapters of this book. Many different types of substance are neurotransmitters. Classical neurotransmitters, such as ACh (see Ch. 11) and norepinephrine (NE see Ch. 12), are low-molecular-weight substances that have no other function but to serve as neurotransmitters. The predominant excitatory neurotransmitter in the brain, glutamate, and the inhibitory neurotransmitter in the spinal cord, glycine, are common and essential amino acids (see Chs 15 and 16). 

BRAIN GLUTAMATE IS DERIVED FROM BLOOD-BORNE GLUCOSE AND AMINO ACIDS THAT CROSS THE BLOOD-BRAIN BARRIER 269... 

Yudkoff, M., Nissim, I., Daikhin, Y. etal. Brain glutamate metabolism neuronal-astroglial relationships. Dev. Neurosci. 15 343-50,1993. 

Haugeto, O., Ullensvang, K., Levy, L. M., Chaudhry, F. A., Honore, T., Nielsen, et al. (1996) Brain glutamate transporter proteins form homomultimers. J. Biol. Chem. 271, 27715-27722. 

Conradt, M. and Stoffel, W. (1997) Inhibition of the high-affinity brain glutamate transporter GLAST-1 via direct phosphorylation../. Neurochem. 68,1244-1251. 

The excitatory neurotransmitter in brain, glutamate, is synthesised from glutamine in a reaction catalysed by the enzyme glntaminase. This enzyme is inhibited by a high concentration of ammonia, which could lead to a chronic depletion of this excitatory neurotransmitter. 

Depletion of glutamate in the glutamine synthetase reaction may have additional effects on the brain. Glutamate and its derivative y-aminobutyrate (GABA see Fig. 22-29) are important neurotransmitters the sensitivity of the brain to ammonia may reflect a depletion of neurotransmitters as well as changes in cellular osmotic balance. ... 

These also presumably lead to a transient quinonoid-carbanionic intermediate. Addition of a proton at the original site of decarboxylation followed by breakup of the Schiff base completes the sequence. Decarboxylation of amino acids is nearly irreversible and frequently appears as a final step in synthesis of amino compounds. For example, in the brain glutamic acid is decarboxy-lated to y-aminobutyric acid (Gaba),193 196b while 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxy-... 

Daikhin Y. and Yudkolf M. (2000). Compartmentation of brain glutamate metabolism in neurons and glia. J. Nutr. 130 1026S-1031S. 

Casado M., Bendahan A., ZafraF., DanboltN. C., Aragon C., Gimenez C., and Kanner B. I. (1993). Phosphorylation and modulation of brain glutamate transporters by protein kinase C. J. Biol. Chem. 268 27313-27317. 

Yudkoff M, Daikhin Y, Nissim I, et al. Ketogenic diet, brain glutamate metabolism and seizure control. 

The rat brain glutamate transporter has been purified to homogeneity (Danbolt et al., 1990) and cloned (Pines et al., 1992). The cloned and expressed transporter showed an absolute dependence on external Na+ and internal K+ consistent with the behavior of the native carrier. 

Glutamate is the primary excitatory neurotransmitter in the brain. Glutamate is formed by the Krebs cycle and is found free and stored in vesicles in synaptic terminals. Its release is calcium dependent, and an uptake system exists in presynaptic terminals and in glia to terminate its action after release. It is possible that glia metabolize glutamate to glutamine and return it to the neuron for reuse. An excessive release of glutamate can be lethal to cells in the immediate vicinity. 

Page MG, Ankoma-Sey V, Coulson WF, and Bender DA (1989) Brain glutamate and gamma-amlnohutyrate (GABA) metaholism in thiamin-deficient rats. British Journal of Nutrition 62, 245-53. 

Figure 32.18. Schematic Structure of a Metabotrophic Glutamate Receptor. The umami receptor is a variant of a brain glutamate receptor. A substantial part of the high-affinity glutamate-binding domain (shown in yellow) is missing in the form expressed in the tongue.

Seeburg PH, Higuchi M, Sprengel R (1998) RNA editing of brain glutamate receptor channels mechanism and physiology. Brain Res Rev 26 217-229. 

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