Insights into the role of d ‐amino acid oxidase mutations in amyotrophic lateral sclerosis

2018 ◽  
Vol 120 (2) ◽  
pp. 2180-2197 ◽  
Author(s):  
Aditya K. Padhi ◽  
Saugata Hazra
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Amino Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Lateral Sclerosis

scholarly journals Questioning on the role of D amino acid oxidase in familial amyotrophic lateral sclerosis

2010 ◽  
Vol 107 (26) ◽  
pp. E107-E107 ◽  
Author(s):  
S. Millecamps ◽  
S. Da Barroca ◽  
C. Cazeneuve ◽  
F. Salachas ◽  
P.-F. Pradat ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Amino Acid ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Lateral Sclerosis

Pathogenic effects of amyotrophic lateral sclerosis-linked mutation in D-amino acid oxidase are mediated by D-serine

2014 ◽  
Vol 35 (4) ◽  
pp. 876-885 ◽  
Author(s):  
Praveen Paul ◽  
Tytus Murphy ◽  
Zainab Oseni ◽  
Suganthinie Sivalokanathan ◽  
Jacqueline S. de Belleroche
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Amino Acid ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Lateral Sclerosis ◽  
Pathogenic Effects

scholarly journals Mechanistic insights into the loss-of-function mechanisms of rare human D-amino acid oxidase variants implicated in amyotrophic lateral sclerosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Aditya K. Padhi ◽  
Kam Y. J. Zhang
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Amino Acid ◽  
Active Site ◽  
Functional Characterization ◽  
Acid Oxidase ◽  
Missense Mutations ◽  
Salt Bridges ◽  
Amino Acid Oxidase ◽  
Structural Dynamic ◽  
Lateral Sclerosis

Abstract Impaired enzymatic activity in D-amino acid oxidase (DAAO) caused by missense mutations has been shown to trigger amyotrophic lateral sclerosis (ALS) through an abnormal accumulation of D-serine in the spinal cord. While loss of enzymatic functions of certain ALS-causing DAAO variants have been studied before, a detailed understanding of structure-dynamics-function relationship of the rare DAAO variants has not been investigated hitherto. To address this, we carried out a comprehensive study of all the reported rare DAAO variants. By employing a spectrum of bioinformatics analyses along with extensive structural dynamics simulations, we show that certain rare variants disrupted key interactions with the active site and decreased the conformational flexibility of active site loop comprising residues 216–228, which is essential for substrate binding and product release. Moreover, these variants lost crucial interactions with the cofactor flavin-adenine-dinucleotide, resulting in weaker binding affinity. A detailed inspection revealed that these variants exhibited such characteristics due to the abrogation of specific salt bridges. Taken together, our study provides a gateway into the structural-dynamic features of the rare DAAO variants and highlights the importance of informatics-based integrated analyses in the screening and prioritization of variants a priori to the clinical-functional characterization.

scholarly journals Biological role of D-amino acid oxidase and D-aspartate oxidase. Effects of D-amino acids.

1993 ◽  
Vol 268 (36) ◽  
pp. 26941-26949
Author(s):  
A D'Aniello ◽  
G D'Onofrio ◽  
M Pischetola ◽  
G D'Aniello ◽  
A Vetere ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Biological Role ◽  
Acid Oxidase ◽  
Amino Acid Oxidase

scholarly journals Role of l-amino acid oxidase isolated from Calloselasma rhodostoma venom on neutrophil NADPH oxidase complex activation

Toxicon ◽  
2018 ◽  
Vol 145 ◽  
pp. 48-55 ◽  
Author(s):  
Mauro Valentino Paloschi ◽  
Charles Nunes Boeno ◽  
Jéssica Amaral Lopes ◽  
André Eduardo dos Santos da Rosa ◽  
Weverson Luciano Pires ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nadph Oxidase ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Nadph Oxidase Complex ◽  
Calloselasma Rhodostoma

D-Serine metabolism: new insights into the modulation of D-amino acid oxidase activity

2013 ◽  
Vol 41 (6) ◽  
pp. 1551-1556 ◽  
Author(s):  
Silvia Sacchi
Keyword(s):  
Enzyme Activity ◽  
Amino Acid ◽  
Oxidase Activity ◽  
Acid Oxidase ◽  
Endogenous Ligand ◽  
Amino Acid Oxidase ◽  
The Brain ◽  
Serine Metabolism ◽  
Synthesis And Degradation

Over the years, accumulating evidence has indicated that D-serine represents the main endogenous ligand of NMDA (N-methyl-D-aspartate) receptors. In the brain, the concentration of D-serine stored in cells is defined by the activity of two enzymes: serine racemase (responsible for both the synthesis and degradation) and D-amino acid oxidase (which catalyses D-serine degradation). The present review is focused on human D-amino acid oxidase, discussing the mechanisms involved in modulating enzyme activity and stability, with the aim to substantiate the pivotal role of D-amino acid oxidase in brain D-serine metabolism.

The formation of choleglobin and the role of catalase in the erythrocyte

1949 ◽  
Vol 136 (884) ◽  
pp. 435-448 ◽  
Keyword(s):  
Hydrogen Peroxide ◽  
Ascorbic Acid ◽  
Amino Acid ◽  
Catalase Activity ◽  
Acid Oxidase ◽  
Small Decrease ◽  
Amino Acid Oxidase ◽  
Oxidase System ◽  
Inverse Proportion

In haemolysates of non-nucleated erythrocytes there is an inverse proportion between catalase activity and rate of choleglobin formation on addition of ascorbic acid. In the intact erythrocytes catalase protects haemoglobin against oxidation and further destruction by the hydrogen peroxide generated by the D-amino-acid oxidase system or by physiological concentrations of ascorbic acid and glutathione. Acid destromatization of haemolyzed horse erythrocytes causes a small decrease in the catalase activity and an increased rate of inactivation of the remaining catalase by ascorbic acid. The liberation of copper from haemocuprein is quantitatively insufficient to explain the decreased stability of the catalase. Exposing duck oxyhaemoglobin, but not reduced haemoglobin, to a pH of 5⋅5 to 5⋅8, causes an alteration which is apparent from the increase of the rate of choleglobin formation. The mechanism of this alteration is discussed. It partly explains the 'stroma effect', at least in duck erythrocytes. In addition, in the latter, there is a true stroma effect. Choleglobin formation in the presence of ascorbic acid is accelerated by a variety of substances. Some of these perturb haemoglobin, while others increase the formation of hydrogen peroxide from ascorbic acid. The implications of our findings on the mechanism of choleglobin formation and on the role of catalase in the erythrocyte are discussed.

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