N- aspartates

McGee AW, Bredt DS (2003) Assembly and plasticity of the glutamatergic postsynaptic specialization. Curr Opin Neurobiol 13 111-118 McRoberts JA, Coutinho SV, Marvizon JC, et al (2001) Role of peripheral N-methyl-n-aspartate (NMDA) receptors in visceral nociception in rats. Gastroenterology 120 1737-1748... 

Mealing GAR, Lanthorn TH, Small DL, et al (1997) Antagonism of N-methyl-n-aspartate-evoked currents in rat cortical cultures by ARE 15896AR. J Pharmacol Exp Ther 281 376-383... 

Wang Y, Small DL, Stanimhovic DB, et al (1997) AMPA receptor-mediated regulation of a Gi-protein in cortical neurons. Nature 389 502-504 Warncke T, Jorimi E, Stubhaug A (1997) Local treatment with the N-methyl-n-aspartate receptor antagonist ketamine, inhibit development of secondary hyperalgesia in man by a peripheral action. Neurosci Lett 227 1-4... 

Cannabinoids may also cause effects via mechanisms distinct from the cannabinoid receptor pathways. The most extensively investigated compound is (+)-HU 211, a synthetic cannabinoid with a stereochemistry opposite to that present in the naturally occurring compounds. It does not produce THC-type effects in animals and shows insignificant binding to the CB, receptor. However, HU 211 blocks A-methyl-n-aspartate (NMDA) receptors and calcium uptake through the NMDA-receptor-ion channel in primary cell cultures. HU 211 is a potent blocker of NMDA-induced tremor, seizures, and lethality in mice. It may therefore prove useful as a nonpsychoactive drug that protects against NMDA-receptor-mediated neurotoxicity. This is supported by the potent attenuation of NMDA-receptor-mediator neurotoxicity in cell cultures by HU 211. 

Glutamate ionotropic receptor (Glu-R) — N-iriethyl-n-aspartate (NMDA)- binding Glu-R (NMDA-Glu-R)... 

Amino acid racemases have long been known to be important in bacterial metabolism, because several u-amino acids are required for the synthesis of cell wall mucopolysaccharides. u-Serine is found in relatively large amounts in mammalian brain, where it acts as an agonist of the N-methyl-n-aspartate (NMDA) glutamate receptor. Serine racemase has been purified from rat brain and cloned fromhuman brain (Wolosker et al., 1999 De Miranda et al., 2000). 

This shows that three more constraints are needed. If we view the three reactions as the points of a triangle, we can view the three constraints as the sides of the triangle. There are a number of ways to do this, but the three constraints used here are coni n(atp) + n(asparagineL) con2 n(atp) -t- n(glutamate) con3 n(aspartate) + n(ppi)... 

Labeled nitrogen. Purine biosynthesis is allowed to take place in the presence of [i N]aspartate, and the newly synthesized GTP and ATP are isolated. What positions are labeled in the two nucleotides ... 

No effective treatment is known. Drugs that counteract the effect of glycine on neuronal cells, such as strychnine, diazepam, and dextromethorphan, could bring mild benefits in milder forms of the condition. Ketamine, an anesthetic blocker of the N-methyl-n-aspartate (NMDA) receptor channel, brought a partial improvement of neurological symptoms and EEG findings m some patients, but their developmental milestones were delayed. 

CNS receptors (e.g, N-Methyl-n-aspartic Endothelial cells of the blood-brain... 

Salvatore, F., Cimino, F., d Ayello-Caracciolo, M., and Cittadini, D., Mechanism of the protection by L-ornithine-n-aspartate mixture and by L-arginine in ammonia intoxication. Arch. Biochcm. Biophys. 107, 499-503 (1964). 

Two observations indicate that aspartate is formed primarily by a transamination reaction, probably from glutamate, rather than by a direct amination with NH4 in A. cylindrica. First, N-label in aspartate was reduced more than 90% by the presence of aminooxy acetate, while labeling of glutamate and glutamine was not reduced (IS). Second, [ N]aspartate was not detected when glutamate formation was inhibited either directly, by azaserine, or indirectly, when glutamine s)mthesis was inhibited by methionine sulfoximine (13). Moreover, activity of a glutamate-aspartate aminotransferase reaction has been detected in vitro in two strains of A. cylindrica (1,26). 

Commercial preparations of pig heart glutamate-oxaloacetate transaminase have been screened for their ability to transaminate various a-keto acids with l-[ N]glutamate (32). In addition to l-[ N]aspartate, enzyme preparations were able to catalyze the formation of labeled tyrosine, phenylalanine, leucine, and dihydroxyphenylalanine, as demonstrated by HPLC (17). However, these amino acids have not yet been obtained in radiopure form by this method. The -keto acid analogs of valine and tryptophan were not transaminated by the enzyme preparations. Glutamate-oxaloacetate transaminases obtained from several commercial sources have varying abilities to transaminate the -keto acid... 

Carles, C. Bies-Etheve, N. Aspart, L. Leon-Kloosterziel, K.M. Koornneef, M. Echeverria, M. Delseny, M. (2002). Regulation of Arabidopsis thaliana Em genes Role of ABI5. Plant Journal, Vol.30, No.3, (May 2002), pp. 373-383, ISSN 0960-7412 Casson, S.A. Lindsey, K (2006). The turnip mutant of Arabidopsis reveals that LEAFY COTYLEDONl expression mediates the effects of auxin and sugars to promote embryonic cell identity. Plant Physiology, Vol.142, No.2, (October 2006), pp. 526-541, ISSN 0032-0889... 

Zaczek, R., Collins, J, and Coyle, J. T., 1981, JV-methyl-n-aspartic acid a potent convulsant with weak neurotoxic properties, Neurosci. Lett., 24 181-186. 

Potentiation by axiracetam was specific for a-amino - 3 - hydroxy - 5 - methyl - 4 - isoxazolepropionic acid (AMPA) receptor-mediated signal transduction, as the drug changed neither the stimulation of Ca influx by kainate or N-methyl-n-aspartate nor the activation of inositol phosphohpid hydrolysis elicited by quisqualate or ( )-l-aminocyclopen-tane-fra s-l,3-dicarboxyhc acid. Piracetam, anira-... 

Monocular deprivation of visual input for 2,7, or 14 consecutive days in new-born Long Evens rats caused p53 accumulation, cell death, and a progressive loss of neurones in the dorsal lateral geniculate nucleus (Nucci etal. 2000). N -Nitro-L-arginine, an inhibitor of NO synthesis, and N-methyl-n-aspartate and other glutamate receptor antagonists prevented these lesions. Finally, poly-(ADP-ribose) polymerase knock-out mice appeared to be protected from monocular deprivation-induced cell death. 

Aspartase. The first of the simple deaminases to be described was aspartase, the enzyme that converts n-aspartate to fumarate and ammonia (I). This enzyme has been found in microorganisms and plants,... 

Ti-Aspartic Oxidase. Aspartase and transaminases account for a major part of the metabolism of L-aspartic acid. n-Aspartic acid is oxidized by an enzyme present in liver and kidney. This is an oxidase that converts aspartate to oxalacetate and ammonia while reducing oxygen to hydrogen peroxide. The oxidase was resolved by ammonium sulfate precipitation and dialysis to a protein that could be reactivated by FAD but not by FMN. The enzyme differs from n-amino acid oxidase in its insensitivity to benzoate. The only other known substrate for the partially purified D-aspartic oxidase is D-glutamate, but since the relative rates of oxidation of the two amino acids vary during the preparation of the enzyme, it is... 

D-Aspariic Acid Oxidase. Still et al. reported that rabbit kidney and liver contain a soluble enzyme which catalyzes the aerobic oxidation of D-aspartate to oxalacetate plus NH3 with the formation of hydrogen peroxide. In a later study by Still and Sperling the D-aspartic acid oxidase was resolved and reactivated by the addition of FAD. The purified enzyme showed about one-sixth the activity with D-glutamate this, according to these workers, is best explained by the presence of a D-glu-tamic acid oxidase. The activity of n-aspartic acid oxidase is higher than that of D-amino acid oxidase in rabbit kidney and liver, and they are of the same order of activity in pig kidney. In contrast to pig kidney o-amino acid oxidase, which is inhibited by benzoic acid, the D-aspartic acid oxidase was unaffected. 

Unlike the D-amino acid oxidase of Krebs, the D-aspartic oxidase is not inhibited by benzoate. Once the n-aspartate is deaminated, the residual carbon moiety is completely oxidized by the homogenate preparations. 

Black and Wright (J. Am. Chem. Soc. 76, 2271, 6766 (1953)), have now demonstrated the enzymatic formation of /3-aspartyl phosphate from n-aspartate and ATP and its enzymatic reduction to homoserine by a TPN-dependent enzyme system obtained from yeast. 

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