D-Aspartate oxidase

ASPARTYLCLUCOSAMINIDASE ASPARTATE AMINOTRANSFERASE ASPARTATE AMMONIA-LYASE ASPARTATE CARBAMOYLTRANSFERASE ASPARTATE a-DECARBOXYLASE ASPARTATE /3-DECARBOXYLASE ASPARTATE KINASE d-ASPARTATE OXIDASE ASPARTATE RACEMASE... 

ACYL-CoA DEHYDROGENASES ADENYLYLSULEATE REDUCTASE ALCOHOL OXIDASE AMINE OXIDASES d-AMINO acid DEHYDROGENASE l-AMINO acid DEHYDROGENASE d-AMINO ACID OXIDASE l-AMINO ACID OXIDASE d-ASPARTATE OXIDASE BENZOATE 1,2-DIOXYGENASE... 

D-Aspartate oxidase L-Amino-acid oxidase D-Amino-acid oxidase Amine oxidase (flavin-containing) Amine oxidase (copper-containing) D-Glutamate oxidase Ethanolamine oxidase Putrescine oxidase L-Glutamate oxidase L-Lysine oxidase... 

D-Glutamate(D-aspartate) oxidase L-Aspartate oxidase Glycine oxidase... 

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... 

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. 

Ach, acetylcholine CNS, central nervous system CD, carbidopa COMT, catechol-O-methyltransferase D1, a class of dopamine receptors which includes D, and D5 subtypes D2, a class of dopamine receptors which includes D2, D3, and D4 subtypes DA, dopamine LD, levodopa MAO, monoamine oxidase MD, maintenance dose NMDA, N-methyl-D-aspartate. 

Wake, K., Yamazaki, H., Hanzawa, S., Konno, R., Sakio, H., Niwa, A., Hori, Y. Exaggerated responses to chronic nociceptive stimuli and enhancement of N-methyl-D-aspartate receptor-mediated synaptic transmission in mutant mice lacking D-amino-acid oxidase, Neurosci. Lett. 2001, 297, 25-28. 

List of Abbreviations CD/MRV, Common Disease/Multiple Rare Variants DAAO, D-amino acid oxidase DAOA, D-aminoacid oxidase activator EST, expression sequence tag GEO, Gene Expression Omnibus MAF, minor allele frequency NIMH, National Institute of Mental Health NMDA, N-methyl D-aspartate RT-PCR, reverse transcription-PCR... 

List of Abbreviations Ach, acetylcholine AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid CNS, central nervous system COMT, catechol-O-methyltransferase DA, dopamine DRP-2, dihy-dropyrimidinase-related protein 2 DSM, diagnostic and statistical manual of mental disorders GNAS1, guanine nucleotide-binding protein (G-protein) alpha stimulating activity polypeptide 1 5-HIAA, 5-hydroxyindole acetic acid 5-FIT, serotonin (5-hydroxytryptamine) MAO, monoamine oxidase MHPG, 3-methoxy-4-hydroxyphenylglycol NE, norepinephrine NMDA, N-methyl-D-aspartate PCP, phencyclidine SSRI, selective serotonin reuptake inhibitor SDS, schedule for the deficit syndrome... 

The flavin co-factor is reduced with concomitant oxidation of the amino acid into the corresponding imino acid, which spontaneously hydrolyzes to the a-keto acid and ammonia the flavin co-factor is then reoxidized by molecular oxygen with the production of hydrogen peroxide. Both D- and L-amino acid oxidases deaminate a variety of amino acids, particularly those having a hydrophobic side chain, but are practically inactive on acidic amino acids (which are deaminated by specific glutamate and aspartate oxidases) and are strictly stereospecific. 

Among the enzymes catalyzing oxidations of carbon nitrogen bonds, the amino acid oxidases (AAO, E.C. 1.4.3.x) are the most interesting for synthetic applications. Compared to some specific amino acid oxidases such as aspartate oxidase or glutamate oxidase, the two d- and L-amino acid oxidases (E.C. 1.4.3.2 for l-AAO and E.C. 1.4.3.3 for d-AAO) are advantageous on account of their broad substrate... 

Mechanisms of action of 30, 31 and 32 were probed in various cell lines. Phthalides 30, 31 and 32 prevented cortical neuronal cell death and inhibited the release of several injury surrogate biomarkers induced by KC1 [335], A -methyl-D-aspartate (NMDA) [335], AA [336] and hypoxia/hypoglycemia [337-339], These effects appeared to be related to an increase in NO and PGI2 release from neuronal [340, 341] and cerebral endothelial cells [342], Phthalides 30, 31 and 32 reduced superoxide anion production in a xanthine-xanthine oxidase reaction system [343]. The three phthalides also decreased intracellular Ca2+ level in cortical neuronal cells [344]. Furthermore, phthalides 30, 31 and 32 ameliorated the abnormal activities of several mitochondrial respiratory chain complexes induced by MCAO [322] and those of mitochondrial ATPase induced by hypoxia/hypoglycemia in cortical neuronal cells [345],... 

Overactivation of glutamate receptors can contribute to a wide variety of lesions, including acute pulmonary oedema (Said et al. 1996), airway hyperesponsiveness (Said 1999) and inflammation. Blocking of the N-methyl-D-aspartate subtype of glutamate receptors by dizocilpine maleate (MK-801 10 pM) attenuated oxidant injury induced by paraquat (100 mg/kg to the pulmonary circulation) or by xanthine oxidase (Said et al. 2000). 

D-Amino Acid Oxidase. The D-amino acid oxidizing activity is the more active and, under ordinary handling, the more stable. Purification studies indicate that a single enzyme, D-amino acid oxidase, is responsible for essentially all oxidation of D-amino acids in animal preparations, although specific enzymes appear to attack D-aspartic and D-glutamic acids. D-Amino acid oxidase was the first enzyme to be resolved into a protein and flavin adenine dinucleotide (FAD). The enzyme, precipitated with acid ammonium sulfate, is active only in the presence of FAD, and is used for both qualitative and quantitative determination of this cofactor. 

The enzyme systems to be considered here are those which are relatively specific for a single amino acid and which yield ammonia as a result of the primary oxidation. Only three systems have been investigated sufficiently to warrant inclusion at this time glutamic acid dehydrogenase, glycine oxidase, and D-aspartic acid oxidase. 

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. 

The D-aspartic acid oxidase of Still and co-workers is found in rabbit kidney as well as liver and is a soluble enzyme which can be obtained in high concentration in the supernatant fluid of the homogenates. Although no soluble coenzyme requirement has been found for the oxidase, it forms H2O2, which suggests that it is a firmly bound flavoprotein. 

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