scholarly journals Ultrastructural localization of D-amino acid oxidase in microperoxisomes of the rat nervous system.

1979 ◽  
Vol 27 (3) ◽  
pp. 735-745 ◽  
Author(s):  
G Arnold ◽  
L Liscum ◽  
E Holtzman
Keyword(s):  
Nervous System ◽  
Amino Acid ◽  
Kojic Acid ◽  
Ultrastructural Localization ◽  
Cell Types ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Marked Diminution ◽  
Biochemical Studies ◽  
System Cell

A recently developed procedure for the localization of D-amino acid oxidase (D-AAO) has been used to investigate the distribution of this enzyme in rat nervous tissue. Initial studies were carried out on kidney to validate the methods. The cytochemically demonstrable enzyme in kidney is inhibited by kojic acid, a known competitive D-AAO inhibitor. Omission of the catalse inhibitor, aminotriazole, from the cytochemical medium produces a marked diminution of D-AAO reaction product in kidney peroxisomes. This would be expected if catalase and D-AAO are present in the same particles. In brain, kojic acid-inhibitable D-AAO is demonstrable in numerous bodies within astrocytes especially in the cerebellum, a brain region known from biochemistry to contain particularly high levels of the oxidase. In preparations incubated for catalase, far fewer positive bodies are seen in the cerebellum. Moreover, omission of aminotriazole has little evident effect on the D-AAO reaction. Thus, the oxidase-containing cerebellar bodies may be relatively poor in catalse. In contrast, several nervous system cell types that contain relatively numerous catalase-positive bodies, contain none with detectable D-AAO. Such heterogeneity of peroxisome enzyme content is in accord with reports from biochemical studies of brain.

scholarly journals Localization of D-amino acid oxidase on the cell surface of human polymorphonuclear leukocytes

1978 ◽  
Vol 77 (1) ◽  
pp. 59-71 ◽  
Author(s):  
JM Robinson ◽  
RT Briggs ◽  
MJ Karnovsky
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cell Surface ◽  
Polymorphonuclear Leukocytes ◽  
Ultrastructural Localization ◽  
H2o2 Production ◽  
Acid Oxidase ◽  
Resting Cells ◽  
Amino Acid Oxidase ◽  
Human Polymorphonuclear Leukocytes

The ultrastructural localization of D-amino acid oxidase (DAO) was studied cytochemically by detecting sites of hydrogen peroxide production in human polymorphonuclear leukocytes (PMNs). Reaction product, which forms when cerous ions react with H2O2 to form an electron-dense precipitate, was demonstrated on the cell surface and within the phagosomes of phagocytically stimulated cells when D-amino acids were provided as substrate. Resting cells showed only slight activity. The competitive inhibitor D,L-2-hydroxybutyrate greatly reduced the D-amino acid-stimulated reaction while KCN did not. The cell surface reaction was abolished by nonpenetrating inhibitors of enzyme activity while that within the phagosome was not eliminated. Dense accumulations of reaction product were formed in cells which phagocytosed Staphylococcus aureus in the absence of exogenous substrate. No reaction product formed with Proteus vulgaris while an intermediate amount formed when Escherichia coli were phagocytosed. Variation in the amount of reaction product with the different bacteria correlated with the levels of D-amino acids in the bacterial cell walls which are available for the DAO of PMNs. An alternative approach utilizing ferricyanide as an electron acceptor was also used. This technique verified the results obtained with the cerium reaction, i.e., the DAO is located in the cell surface and is internalized during phagocytosis and is capable of H2O2 production within the phagosome. The present finding that DAO is localized on the cell surface further supports the concept that the plasma membrane is involved in peroxide formation in PMNs.

scholarly journals D-aspartate oxidation by rat and bovine renal peroxisomes: an electron microscopic cytochemical study.

1990 ◽  
Vol 38 (9) ◽  
pp. 1377-1381 ◽  
Author(s):  
M E Beard
Keyword(s):  
Amino Acid ◽  
Oxidase Activity ◽  
Electron Microscopic Level ◽  
Acid Oxidase ◽  
Electron Microscopic ◽  
Amino Acid Oxidase ◽  
Cytochemical Localization ◽  
Peroxisomal Enzyme ◽  
Cytochemical Study ◽  
Biochemical Studies

D-amino acid oxidase, a peroxisomal enzyme, and D-aspartate oxidase, a potential peroxisomal enzyme, share biochemical attributes. Both produce hydrogen peroxide in flavin-requiring oxidative reactions. Such similarities suggest that D-aspartate oxidase may also be localized to peroxisomes. Definitive identification of D-aspartate oxidase as a peroxisomal enzyme depends, however, on visualization at the electron microscopic level. Using incubation conditions shown to be specific for the enzyme in biochemical studies, this report extends the cytochemical localization of D-amino acid oxidase to bovine renal peroxisomes, and shows that D-aspartate can be oxidized by rat and bovine renal peroxisomes. An unexpected finding was the sensitivity of both D-amino acid oxidase activity (proline specific) and D-aspartate oxidase activity to inhibition by agents used in biochemical studies to discriminate between the two enzyme activities. Therefore, it is possible that, in the cytochemical system used in this study, (a) either D-proline and D-aspartate are substrates for only one enzyme or (b) the two enzymes have additional overlapping biochemical properties.

Free d-serine, d-aspartate and d-alanine in central nervous system and serum in mutant mice lacking d-amino acid oxidase

1993 ◽  
Vol 152 (1-2) ◽  
pp. 33-36 ◽  
Author(s):  
Atsushi Hashimoto ◽  
Toru Nishikawa ◽  
Ryuichi Konno ◽  
Akira Niwa ◽  
Yosihiro Yasumura ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Mutant Mice ◽  
Acid Oxidase ◽  
Amino Acid Oxidase

scholarly journals Characterization of a Yeastd-Amino Acid Oxidase Microbiosensor ford-Serine Detection in the Central Nervous System

2008 ◽  
Vol 80 (5) ◽  
pp. 1589-1597 ◽  
Author(s):  
Pierre Pernot ◽  
Jean-Pierre Mothet ◽  
Oleg Schuvailo ◽  
Alexey Soldatkin ◽  
Loredano Pollegioni ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
The Central Nervous System

scholarly journals Salmonella Evades d-Amino Acid Oxidase To Promote Infection in Neutrophils

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Brian R. Tuinema ◽  
Sarah A. Reid-Yu ◽  
Brian K. Coombes
Keyword(s):  
Amino Acid ◽  
Cell Types ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Bacterial Killing ◽  
Host Pathogen Interaction ◽  
Early Stages ◽  
Host Pathogen ◽  
Novel Host

ABSTRACTNeutrophils engulf and kill bacteria using oxidative and nonoxidative mechanisms. Despite robust antimicrobial activity, neutrophils are impaired in directingSalmonellaclearance and harbor viable intracellular bacteria during early stages of infection that can subsequently escape to more-permissive cell types. The mechanisms accounting for this immune impairment are not understood. We report thatSalmonellalimits exposure to oxidative damage elicited byd-amino acid oxidase (DAO) in neutrophils by expressing an ABC importer specific ford-alanine, a DAO substrate found in peptidoglycan stem peptides. ASalmonella dalSmutant defective ford-alanine import was more susceptible to killing by DAO through exposure to greater oxidative stress during infection. This fitness defect was reversed by selective depletion of neutrophils or by inhibition of DAOin vivowith a small-molecule inhibitor. DalS-mediated subversion of neutrophil DAO is a novel host-pathogen interaction that enhancesSalmonellasurvival during systemic infection.IMPORTANCENeutrophils engulfSalmonelladuring early stages of infection, but bacterial killing is incomplete. Very little is known about howSalmonellasurvives in neutrophils to gain access to other cell types during infection. In this study, we show thatd-amino acid oxidase (DAO) in neutrophils consumesd-alanine and that importing this substrate protectsSalmonellafrom oxidative killing by neutrophil DAO. Loss of this importer results in increased bacterial killingin vitro, in neutrophils, and in a mouse model of infection, all phenotypes that are lost upon inhibition of DAO. These findings add mechanistic insight into a novel host-pathogen interaction that has consequences on infection outcome.

scholarly journals Human D-aspartate Oxidase: A Key Player in D-aspartate Metabolism

2021 ◽  
Vol 8 ◽  
Author(s):  
Loredano Pollegioni ◽  
Gianluca Molla ◽  
Silvia Sacchi ◽  
Giulia Murtas
Keyword(s):  
Amino Acids ◽  
Nervous System ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Tertiary Structure ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Acid Oxidase ◽  
Oligomeric State ◽  
Amino Acid Oxidase

In recent years, the D-enantiomers of amino acids have been recognized as natural molecules present in all kingdoms, playing a variety of biological roles. In humans, d-serine and d-aspartate attracted attention for their presence in the central nervous system. Here, we focus on d-aspartate, which is involved in glutamatergic neurotransmission and the synthesis of various hormones. The biosynthesis of d-aspartate is still obscure, while its degradation is due to the peroxisomal flavin adenine dinucleotide (FAD)-containing enzyme d-aspartate oxidase. d-Aspartate emergence is strictly controlled: levels decrease in brain within the first days of life while increasing in endocrine glands postnatally and through adulthood. The human d-aspartate oxidase (hDASPO) belongs to the d-amino acid oxidase-like family: its tertiary structure closely resembles that of human d-amino acid oxidase (hDAAO), the enzyme that degrades neutral and basic d-amino acids. The structure-function relationships of the physiological isoform of hDASPO (named hDASPO_341) and the regulation of gene expression and distribution and properties of the longer isoform hDASPO_369 have all been recently elucidated. Beyond the substrate preference, hDASPO and hDAAO also differ in kinetic efficiency, FAD-binding affinity, pH profile, and oligomeric state. Such differences suggest that evolution diverged to create two different ways to modulate d-aspartate and d-serine levels in the human brain. Current knowledge about hDASPO is shedding light on the molecular mechanisms underlying the modulation of d-aspartate levels in human tissues and is pushing novel, targeted therapeutic strategies. Now, it has been proposed that dysfunction in NMDA receptor-mediated neurotransmission is caused by disrupted d-aspartate metabolism in the nervous system during the onset of various disorders (such as schizophrenia): the design of suitable hDASPO inhibitors aimed at increasing d-aspartate levels thus represents a novel and useful form of therapy.

scholarly journals Synthesis of kojic acid derivatives as secondary binding site probes of d-amino acid oxidase

2013 ◽  
Vol 23 (13) ◽  
pp. 3910-3913 ◽  
Author(s):  
Mithun Raje ◽  
Niyada Hin ◽  
Bridget Duvall ◽  
Dana V. Ferraris ◽  
James F. Berry ◽  
...  
Keyword(s):  
Amino Acid ◽  
Binding Site ◽  
Kojic Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase
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