Glutamic acid transport

Kanner, B. I. and Bendahan, A. (1982) Binding order of substrates to the sodium and potassium ion coupled L-glutamic acid transporter from rat brain. Biochemistry 21,6327-6330. 

A direct K+ requirement for translocation has, however, been reported for glutamic acid transport in brain (Kanner and Schuldiner, 1987 Carlson et al., 1989). The dicarboxylic amino acids appear to be transported largely by specific transporters which do not participate in neutral amino acid transport. Recent studies, both in reconstituted systems and the expression of the cloned transporter, have confirmed the K+ requirement (see below). 

Berteloot A. Cation, pH and membrane-potential dependencies of intestinal glutamic-acid transport. Federation Proc. 1985 44 444. 

Kanai Y, Hediger MA (2004) The glutamate/neutral amino acid transporter family SLC1 molecular, physiological and pharmacological aspects. Pfliigers Arch 447 469-479... 

Orexin neurons, likely to be glutamatergic themselves, express the excitatory amino acid transporter EAAT3, vesicular glutamate transporters VGLUT1 and VGLUT2, secretogranin II, ionotropic (NMDAR,... 

HIV proteins can also disrupt ion homeostasis in astrocytes, which compromises neuronal function (Pulliam et al. 1993 Benos et al. 1994a, b Holden et al. 1999). Intact HIV-1 virions or gpl20 also markedly inhibit glutamate uptake by astrocytes and cause reductions in excitatory amino acid transporter-2 (EAAT2) mRNA and protein levels (Wang et al. 2003). The inability of astrocytes to buffer extracellular glutamate is likely to decrease the excitotoxic threshold of bystander neurons. 

If a substance is to be a NT it should be possible to demonstrate appropriate enzymes for its synthesis from a precursor at its site of action, although peptides are transported to their sites of location and action after synthesis in the axon or distal neuronal cell body. The specificity of any enzyme system must also be established, especially if they are to be modified to manipulate the levels of a particular NT, or used as markers for it. Thus choline acetyltransferase (ChAT) may be taken as indicative of ACh and glutamic acid decarboxylase (GAD) of GABA but some of the synthesising enzymes for the monoamines lack such specificity. 

J Liaw, Y Rojanasakul, JR Robinson. (1991). The effect of charge type and charge density on corneal transport of lysine and glutamic acid—Evidence for active transport. Pharm Res 8(Suppl) S-130. 

Jacocks, H.M. and Cox, B.K., Serotonin-stimulated [3H]dopamine via reversal of the dopamine transporter in rat striatum and nucleus accumbens a comparison with release elicited by potassium, N-methyl-D-aspartic acid, glutamic acid and D-amphetamine, J. Pharmacol. Exp. Ther., 262, 356, 1992. 

The other subfamily, SLC1, includes the Na+-dependent glutamate transporters. It encompasses some amino- and carboxylic-acid transporters including glutamate transporters that are expressed in bacteria. X-ray diffraction data have been obtained from crystals of one of these [43] (Fig. 5-13). Analysis of multiple sequence alignments indicates that this molecule has a high degree of structural... 

Excitotoxicity (see Chs 15 and 32) has been suggested to be a mechanism by which motor neurons are damaged in ALS [25,48,49]. About 60-70% of sporadic ALS patients have a 30-95% reduction in the levels of the astroglial glutamate transporter EAAT2 (excitatory amino acid transporter 2), also termed GLT-1, in motor cortex and spinal cord [25, 48, 49]. Reduction in level of activity of this major glutamate transporter leads to increased extracellular concentrations of glutamate at synapses and evidence of excitotoxicity exists in some patients with ALS. 

Arriza, J. L., Eliasof, S., Kavanaugh, M. P., and Amara, S. G. (1997) Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc. Natl. Acad. Sci USA 94,4155 1160. 

Shafqat, S., Tamarappoo, B. K., Kilberg, M. S., Puranam, R. S., McNamara, J. O., Guadano-Ferraz, A., and Fremeau, R. T. (1993) Cloning and expression of a novel Na+-dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters. J. Biol. Chem. 268,15351-15355. 

Luruta, A., Martin, L. J., Lin, C. L Dykes-Hoberg, M., and Rothstein, J. D. (1997) Cellular and synaptic localization of the neuronal glutamate transporters excitatory amino acid transporter 3 and 4. Neuroscience 81,1031-1042. 

Loland, C. J., Norregaard, L., and Gether, U. (1999) Defining proximity relationships in the tertiary structure of the dopamine transporter. Identification of a conserved glutamic acid as a third coordinate in the endogenous Zn(2+)-binding site. J. Biol. Chem. 274, 36928-36934. 

Molecular Neuropharmacology Strategies and Methods is intended to bridge the gap between molecular biology and advanced chemistry. In addition, it attempts to include information about x-ray crystallographic analyses whenever available. This book discusses interdisciplinary interactions for monoamine transporters, amino acid transporters, ionotropic receptors, metabotropic glutamate receptors, GABA receptors, and other G protein-coupled receptors. 

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