MOUSE MUTANT DEFICIENT IN d-AMINO ACID OXIDASE ACTIVITY

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

Biochemical Society Transactions ◽

10.1042/bst20130184 ◽

2013 ◽

Vol 41 (6) ◽

pp. 1551-1556 ◽

Cited By ~ 10

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.

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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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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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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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The Effect of Castration and Testosterone Propionate on d-Amino Acid Oxidase Activity in the Mouse

Science ◽

10.1126/science.98.2534.89.a ◽

1943 ◽

Vol 98 (2534) ◽

pp. 89-89

Author(s):

L. C. Clark ◽

C. D. Kochakian ◽

R. Phyllis Fox

Keyword(s):

Amino Acid ◽

Oxidase Activity ◽

Testosterone Propionate ◽

Acid Oxidase ◽

Amino Acid Oxidase

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Production ofD-amino acid oxidase byAspergillussp. strain O20 active on cephalosporin C

Canadian Journal of Microbiology ◽

10.1139/m97-040 ◽

1997 ◽

Vol 43 (3) ◽

pp. 292-295 ◽

Cited By ~ 2

Author(s):

Salim K. Mujawar ◽

Jaiprakash G. Shewale

Keyword(s):

Amino Acids ◽

Enzyme Activity ◽

Amino Acid ◽

Stationary Growth Phase ◽

Acid Oxidase ◽

Cephalosporin C ◽

Production Medium ◽

Stationary Growth ◽

Amino Acid Oxidase ◽

Aspergillus Sp

Aspergillus sp. strain O20 produces inducible D-amino acid oxidase intracellularly, only in the presence of some amino acids. The enzyme was induced most effectively by the addition of DL-alanine (1% w/v) to the production medium. Among the various compounds studied, production of the D-amino acid oxidase was enhanced by Aerosol-22, glucose, and sodium nitrate. D-Amino acid oxidase formation was observed during the onset of the stationary growth phase. Maximum enzyme activity was recorded after 96 h of fermentation (1000 IU/L).Key words: D-amino acid oxidase, Aspergillus sp., 7-aminocephalosporanic acid, cephalosporin C.

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Multipoint TvDAAO Mutants for Cephalosporin C Bioconversion

International Journal of Molecular Sciences ◽

10.3390/ijms20184412 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4412

Author(s):

Denis L. Atroshenko ◽

Mikhail D. Shelomov ◽

Sophia A. Zarubina ◽

Nikita Y. Negru ◽

Igor V. Golubev ◽

...

Keyword(s):

Amino Acid ◽

Thermal Denaturation ◽

Catalytic Properties ◽

Acid Oxidase ◽

Cephalosporin C ◽

Wild Type ◽

Wild Type Enzyme ◽

Amino Acid Oxidase ◽

Catalytic Constant ◽

Biotechnological Processes

d-amino acid oxidase (DAAO, EC 1.4.3.3) is used in many biotechnological processes. The main industrial application of DAAO is biocatalytic production of 7-aminocephalosporanic acid from cephalosporin C with a two enzymes system. DAAO from the yeast Trigonopsis variabilis (TvDAAO) shows the best catalytic parameters with cephalosporin C among all known DAAOs. We prepared and characterized multipoint TvDAAO mutants to improve their activity towards cephalosporin C and increase stability. All TvDAAO mutants showed better properties in comparison with the wild-type enzyme. The best mutant was TvDAAO with amino acid changes E32R/F33D/F54S/C108F/M156L/C298N. Compared to wild-type TvDAAO, the mutant enzyme exhibits a 4 times higher catalytic constant for cephalosporin C oxidation and 8- and 20-fold better stability against hydrogen peroxide inactivation and thermal denaturation, respectively. This makes this mutant promising for use in biotechnology. The paper also presents the comparison of TvDAAO catalytic properties with cephalosporin C reported by others.

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P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency

The Journal of Biochemistry ◽

10.1093/jb/mvaa083 ◽

2020 ◽

Vol 168 (5) ◽

pp. 557-567

Author(s):

Wanitcha Rachadech ◽

Yusuke Kato ◽

Rabab M Abou El-Magd ◽

Yuji Shishido ◽

Soo Hyeon Kim ◽

...

Keyword(s):

Amino Acid ◽

Conformational Changes ◽

Active Site ◽

Structural Changes ◽

Catalytic Efficiency ◽

Acid Oxidase ◽

Wild Type ◽

Amino Acid Oxidase ◽

Adenine Ring ◽

The Impact

Abstract Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7–0.9 µM) compared with wild-type (1.2–2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure–function relationship of human DAO.

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