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

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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Role of Castration and Androgens in D-Amino Acid Oxidase Activity of Tissues

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1956.185.2.250 ◽

1956 ◽

Vol 185 (2) ◽

pp. 250-256 ◽

Cited By ~ 12

Author(s):

Barbara R. Endahl ◽

Charles D. Kochakian

Keyword(s):

Enzyme Activity ◽

Amino Acid ◽

Guinea Pig ◽

Oxidase Activity ◽

The Other ◽

Maximum Effect ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

Small Doses

A large number of C19 steroids were able to markedly increase the d-amino acid oxidase activity of the kidney of the castrated mouse. The maximum effect was attained within 21 days of treatment and with relatively small doses of the most potent androgens. On the other hand, neither castration nor various androgens were able to significantly alter the d-amino acid oxidase activity of either the kidney or liver of the castrated rat and guinea pig. Furthermore, age did not influence the enzyme activity of the tissues of the rat (2–8 months of age) or the guinea pig (4–8 months of age). Estradiol produced a small increase in the d-amino acid oxidase activity of the kidney of the mouse but estrone, methoxybisdehydrodiosynolic acid and several corticoids were ineffective.

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Determination of free d-aspartic acid, d-serine and d-alanine in the brain of mutant mice lacking d-amino-acid oxidase activity

Journal of Chromatography B Biomedical Sciences and Applications ◽

10.1016/s0378-4347(01)00131-1 ◽

2001 ◽

Vol 757 (1) ◽

pp. 119-125 ◽

Cited By ~ 112

Author(s):

Akiko Morikawa ◽

Kenji Hamase ◽

Tomomi Inoue ◽

Ryuichi Konno ◽

Akira Niwa ◽

...

Keyword(s):

Amino Acid ◽

Aspartic Acid ◽

Oxidase Activity ◽

Mutant Mice ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

The Brain

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MOUSE MUTANT DEFICIENT IN d-AMINO ACID OXIDASE ACTIVITY

Genetics ◽

10.1093/genetics/103.2.277 ◽

1983 ◽

Vol 103 (2) ◽

pp. 277-285 ◽

Cited By ~ 1

Author(s):

Ryuichi Konno ◽

Yosihiro Yasumura

Keyword(s):

Enzyme Activity ◽

Amino Acid ◽

Oxidase Activity ◽

Null Allele ◽

Gene Dosage ◽

Autosomal Gene ◽

Acid Oxidase ◽

Wild Type ◽

Amino Acid Oxidase ◽

Gene Dosage Effect

ABSTRACT d-Amino acid oxidase activity in the kidney homogenates of mice of seven strains was measured to search for a mutant for this enzyme. There was a consistent sex difference in the enzyme activity in these strains: male mice showed higher levels of the enzyme activity than females. In contrast to other strains, some mice of the ddY strain did not possess enzyme activity. This trait was inheritable, and a mouse stock without enzyme activity (DAO-) was established. The allele (Dao-1c) carried by the DAO- mice was recessive and behaved as a single autosomal gene in inheritance. Heterozygous mice for this gene (Dao-1 +/Dao-1c) showed nearly half the enzyme activity of the wild-type homozygotes (Dao-1 +/Dao-1 +), suggesting that Dao-1c is a null allele and that there is a gene dosage effect on the enzyme activity.

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Studies on aromatic amino acid oxidase activity in ram spermatozoa: role of pyruvate as an antioxidant

Animal Reproduction Science ◽

10.1016/s0378-4320(98)00082-7 ◽

1998 ◽

Vol 51 (4) ◽

pp. 275-287 ◽

Cited By ~ 75

Author(s):

G.C. Upreti ◽

K. Jensen ◽

R. Munday ◽

D.M. Duganzich ◽

R. Vishwanath ◽

...

Keyword(s):

Amino Acid ◽

Oxidase Activity ◽

Aromatic Amino Acid ◽

Acid Oxidase ◽

Amino Acid Oxidase

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Variations of l- and d-amino acid levels in the brain of wild-type and mutant mice lacking d-amino acid oxidase activity

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-018-0979-9 ◽

2018 ◽

Vol 410 (12) ◽

pp. 2971-2979 ◽

Cited By ~ 18

Author(s):

Siqi Du ◽

Yadi Wang ◽

Choyce A. Weatherly ◽

Kylie Holden ◽

Daniel W. Armstrong

Keyword(s):

Amino Acid ◽

Oxidase Activity ◽

Mutant Mice ◽

Acid Oxidase ◽

Wild Type ◽

Amino Acid Oxidase ◽

Amino Acid Levels ◽

The Brain

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d-Amino acids in the brain and mutant rodents lacking d-amino-acid oxidase activity

Amino Acids ◽

10.1007/s00726-012-1384-x ◽

2012 ◽

Vol 43 (5) ◽

pp. 1811-1821 ◽

Cited By ~ 29

Author(s):

Masahiro Yamanaka ◽

Yurika Miyoshi ◽

Hiroko Ohide ◽

Kenji Hamase ◽

Ryuichi Konno

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Oxidase Activity ◽

Acid Oxidase ◽

Amino Acid Oxidase ◽

The Brain

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Impairment of Platelet Aggregation by Echis colorata Venom Mediated by L-Amino Acid Oxidase or H2O2

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657280 ◽

1982 ◽

Vol 48 (03) ◽

pp. 277-282 ◽

Cited By ~ 22

Author(s):

I Nathan ◽

A Dvilansky ◽

T Yirmiyahu ◽

M Aharon ◽

A Livne

Keyword(s):

Hydrogen Peroxide ◽

Amino Acid ◽

Platelet Aggregation ◽

Snake Venom ◽

Oxidase Activity ◽

Enzyme Preparation ◽

Acid Oxidase ◽

Crude Venom ◽

Amino Acid Oxidase ◽

Hemostatic Disorders

SummaryEchis colorata bites cause impairment of platelet aggregation and hemostatic disorders. The mechanism by which the snake venom inhibits platelet aggregation was studied. Upon fractionation, aggregation impairment activity and L-amino acid oxidase activity were similarly separated from the crude venom, unlike other venom enzymes. Preparations of L-amino acid oxidase from E.colorata and from Crotalus adamanteus replaced effectively the crude E.colorata venom in impairment of platelet aggregation. Furthermore, different treatments known to inhibit L-amino acid oxidase reduced in parallel the oxidase activity and the impairment potency of both the venom and the enzyme preparation. H2O2 mimicked characteristically the impairment effects of L-amino acid oxidase and the venom. Catalase completely abolished the impairment effects of the enzyme and the venom. It is concluded that hydrogen peroxide formed by the venom L-amino acid oxidase plays a role in affecting platelet aggregation and thus could contribute to the extended bleeding typical to persons bitten by E.colorata.

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