Glutamate and aspartate in brain

McGeer P. L., Eccles J. C., and McGeer E. G. (1987). Putative excitatory neurons Glutamate and aspartate. In McGeer P. L., Eccles J. C., and McGeer E. G. (eds.), Molecular Neurobiology of the Mammalian Brain. Plenum Press, New York. 

Evidence suggests that ketone bodies reduce epileptic seizures by changing the metabolism of certain amino acids (glutamate and aspartate) in the brain (Yudkoff et al., 1997). These two amino adds are neurotransmitters, that is, they act as hormones that relay signals from one nerve to another adjacent nerve. 

As opposed to the two other endogenous excitatory amino acid candidates, cystelc acid and cysteine sulphinlc acid (15), glutamate (16) and aspartate (13) are found in abundant quantities in the mammalian CNS. Metabolically, aspartate and glutamate are related and their metabolism is quite complex. Thus, there are undoubtedly several metabolic pools of glutamate and aspartate, in addition to any neurotransmitter pool, making it difficult to study the biochemical aspects of their neurotransmitter action. Nevertheless, it has been shown that both substances are accumulated into brain tissue by a high affinity process, and that both can be released from brain tissue by electrical field stimulation. This behavior is characteristic of neurotransmitters. 

Van den Berg CJ, Mela P, Waelsch H (1966) On the contribution of the tricarboxylic acid cycle to the synthesis of glutamate, glutamine and aspartate in brain. Biochem Biophys Res Commun 23 479-484. 

Ramos, M., del Arco, A., Pardo, B. etal. Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralarl in brain and prominent expression in the spinal cord. Brain Res. Dev. Brain Res. 143 33-46, 2003. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

The biochemical roles of these processes The metabolism of glutamate and aspartate by the enterocytes provides not only ATP, via oxidation of the oxoacids, but can also be considered to be a detoxification process. Both glutamate and aspartate are neurotransmitters in the brain. If their concentrations in blood increase too much, they could interfere with the control of neurotransmitter levels in the brain with possible changes in behaviour or clinical problems (see below). One such phenomenon is Chinese Restaurant Syndrome , but there may be other problems, as yet not reparted. 

The brain contains several transporters specialized for rapid uptake of neurotransmitters glutamate and aspartate,423-425 glycine,426 y-aminobutyrate (Gaba),427/428 and catecholamines and also for taurine, L-proline,429 serotonin,430 and other substances. Many of these are not only Na+ dependent but also require cotransport of Cl-.428-430 There are several different glutamate transporter genes with specialized distribution in the brain and other tissues.423 424... 

In brain tissue, low concentrations of glutamate and aspartate perform as neurotransmitters, but at high concentration these amino acids act as neurotoxins. Major advances in the excitatory amino acid receptor field have come from the identification, characterization, and cloning of different families of receptors and transporters (Dingledine and McBain, 1999). These receptors and transporters are specialized... 

Phillis J. W. and O Regan M. H. (1996). Mechanisms of glutamate and aspartate release in the ischemic rat cerebral cortex. Brain Res. 730 150-164. 

The heterogeneity of dopaminergic neurons may also be judged by the fact that the cotransmitter systems involving dopamine and peptides are varied in the central nervous system. For example, in the corpus striatum, in addition to dopamine, acetylcholine, y-aminobutyric acid, serotonin, glutamate, and aspartate, one also finds peptides such as enkephalin, substance P, somatostatin, neuropeptide Y, cholecystokinin, neurotensin, and vasoactive intestinal peptide. Although many neuroleptics block dopamine receptors, they may have selective effects on the peptides and other parts of the brain. A few examples will be cited. 

Benzodiazepines enhance presynaptic inhibition by releasing GABA from intemeurons and by facilitating the action of glycine in the spinal cord and brain stem. Glutamate and aspartate have... 

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