Indispensable but Insufficient Role of Renal D-Amino Acid Oxidase in Chiral Inversion of NG-Nitro-D-arginine

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.

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

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1949.0035 ◽

1949 ◽

Vol 136 (884) ◽

pp. 435-448 ◽

Cited By ~ 11

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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Role of renal d-amino-acid oxidase in pharmacokinetics of d-leucine

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00397.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. E160-E165 ◽

Cited By ~ 22

Author(s):

Hiroshi Hasegawa ◽

Takehisa Matsukawa ◽

Yoshihiko Shinohara ◽

Ryuichi Konno ◽

Takao Hashimoto

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Renal Mass ◽

Acid Oxidase ◽

Mass Reduction ◽

Chiral Inversion ◽

Amino Acid Oxidase ◽

Isotope Tracer ◽

Keto Acids

d-Amino acids are now recognized to be widely present in mammals. Renal d-amino-acid oxidase (DAO) is associated with conversion of d-amino acids to the corresponding α-keto acids, but its contribution in vivo is poorly understood because the α-keto acids and/or l-amino acids formed are indistinguishable from endogenous compounds. First, we examined whether DAO is indispensable for conversion of d-amino acids to their α-keto acids by using the stable isotope tracer technique. After a bolus intravenous administration of d-[2H7]leucine to mutant mice lacking DAO activity (ddY/DAO−) and normal mice (ddY/DAO+), elimination of d-[2H7]leucine and formation of α-[2H7]ketoisocaproic acid ([2H7]KIC) and l-[2H7]leucine in plasma were determined. The ddY/DAO− mice, in contrast to ddY/DAO+ mice, failed to convert d-[2H7]leucine to [2H7]KIC and l-[2H7]leucine. This result clearly revealed that DAO was indispensable for the process of chiral inversion of d-leucine. We further investigated the effect of renal mass reduction by partial nephrectomy on elimination of d-[2H7]leucine and formation of [2H7]KIC and l-[2H7]leucine. Renal mass reduction slowed down the elimination of d-[2H7]leucine. The fraction of conversion of d-[2H7]leucine to [2H7]KIC in sham-operated rats was 0.77, whereas that in five-sixths-nephrectomized rats was 0.25. The elimination behavior of d-[2H7]leucine observed in rats suggested that kidney was the principal organ responsible for converting d-leucine to KIC.

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Focus on the Role of D-serine and D-amino Acid Oxidase in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS)

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2018.00008 ◽

2018 ◽

Vol 5 ◽

Cited By ~ 12

Author(s):

Nazanin R. Kondori ◽

Praveen Paul ◽

Jacqueline P. Robbins ◽

Ke Liu ◽

John C. W. Hildyard ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Amino Acid ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

Lateral Sclerosis

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The role of Cys108 in Trigonopsis variabilis d-amino acid oxidase examined through chemical oxidation studies and point mutations C108S and C108D

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics ◽

10.1016/j.bbapap.2010.02.009 ◽

2010 ◽

Vol 1804 (7) ◽

pp. 1483-1491 ◽

Cited By ~ 6

Author(s):

Mario Mueller ◽

Regina Kratzer ◽

Margaretha Schiller ◽

Anita Slavica ◽

Gerald Rechberger ◽

...

Keyword(s):

Amino Acid ◽

Point Mutations ◽

Chemical Oxidation ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

Trigonopsis Variabilis

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Role of d -amino acid oxidase in the production of kynurenine pathway metabolites from d -tryptophan in mice

Journal of Neurochemistry ◽

10.1111/jnc.13455 ◽

2016 ◽

Vol 136 (4) ◽

pp. 804-814 ◽

Cited By ~ 7

Author(s):

Francesca M. Notarangelo ◽

Xiao-Dan Wang ◽

Kyle J. Horning ◽

Robert Schwarcz

Keyword(s):

Amino Acid ◽

Kynurenine Pathway ◽

Acid Oxidase ◽

Amino Acid Oxidase

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Studies on the structural and functional aspects of Rhodotorula gracilisd-amino acid oxidase by limited trypsinolysis

Biochemical Journal ◽

10.1042/bj3100577 ◽

1995 ◽

Vol 310 (2) ◽

pp. 577-583 ◽

Cited By ~ 15

Author(s):

L Pollegioni ◽

F Ceciliani ◽

B Curti ◽

S Ronchi ◽

M S Pilone

Keyword(s):

Amino Acid ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

Compact Structure ◽

Peptide Bonds ◽

Functional Aspects ◽

Complex Forms ◽

Limited Trypsinolysis ◽

Dimerization Process

The structure-function relationships of purified Rhodotorula gracilis D-amino acid oxidase (in its holo-, apo- and holo-enzyme-benzoate complex forms) was analysed by digestion with trypsin. In all cases trypsin cleaves this 80 kDa dimeric enzyme at the C-terminal region, since the peptide bonds sensitive to proteinase attack are clustered in this region. Digestion of native enzyme with trypsin produced a nicked and truncated form of 38.3 kDa containing two polypeptides of 34 and 5 kDa starting from Met1 and Ala319 respectively, and with detachment of the Thr306-Arg318 and Glu365-Leu368 peptides. Our results show that this *#x2018;core’, folded into a compact structure, is catalytically competent. The acquisition of this nicked form was marked by a shift from a dimeric to a monomeric active enzyme, a result never previously obtained. The deleted sequences, Thr306-Arg318 and Glu365-Leu368, are essential for the monomer-monomer interaction, and, in particular, the region encompassing Thr306-Arg318 should play an essential role in the dimerization process. interestingly, the Ser308-Lys321 sequence present in the lost peptide corresponds to a sequence not present in other known D-amino acid oxidases [Faotto, Pollegioni, Ceciliani, Ronchi and Pilone (1995) Biotechnol. Lett. 17, 193-198]. A role of the cleaved-off region for the thermostabilization of the enzyme is also discussed.

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