d-aspartate oxidase of kidney

Dixon, Malcolm; Kenworthy, P.

doi:10.1016/0005-2744(67)90073-3

Cited by 53 publications

(19 citation statements)

References 11 publications

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“…Whereas D-AAOX oxidizes neutral or basic D-amino acids, D-ASPOX specifically catalyzes the oxidation of the D-stereoisomers of the acidic amino acids aspartate and glutamate (D'Aniello et al, I993b;Negri et al, 1987;Hamilton, 1985) and also of stereoisomers of certain other acidic amino or heterocyclic iminoacids (Solinas et al, 1986;Hamilton, 1985;Burns et al, 1984). D-ASPOX transfers electrons either to oxygen, producing hydrogen peroxide, or to other terminal electron acceptors (Negri et al, 1987;Dixon and Kenworthy, 1967).…”

Section: Introductionmentioning

confidence: 99%

Light and electron microscopic localization of D-aspartate oxidase in peroxisomes of bovine kidney and liver: an immunocytochemical study.

Zaar

1996

J Histochem Cytochem.

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D-Aspartate oxidase (EC 1.4.3.1; D-ASPOX) specifically oxidizes the D-isomers of dicarboxylic amino acids such as aspartic or glutamic acid. Subcellular fractionation experiments in the past showed its association with peroxisome preparations in kidney cortex and liver. However, no information exists on the in situ localization and distribution of the enzyme in different cell types. We have purified the enzyme from the bovine kidney and raised an antibody against it in rabbits. The monospecificity of the antibody has been confirmed by Western blotting and it does not crossreact with D-amino, acid oxidase. Immunohistochemical localization of the antigen in bovine kidney and liver with the streptavidin-biotin-peroxidase technique revealed a punctate localization in the epithelial cells of proximal nephron tubules, particularly in the straight P-3 segment, as well as in hepatocytes. This is consistent with a localization in peroxisomes. Best results have been obtained with Carnoy-fixed material after paraffin embedding or after fixation with formaldehyde-glutaraldehyde in cryostat sections. Immunoelectron microscopy with protein A-gold confirms the peroxisomal localization of D-ASPOX. Gold particles are distributed over the matrix, suggestive of a peroxisomal matrix enzyme. This is the first report on the localization of D-ASPOX, a little-known peroxisomal enzyme. The techniques described and the antibody prepared will now allow systematic investigation of its tissue distribution.

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Section: Introductionmentioning

confidence: 99%

Light and electron microscopic localization of D-aspartate oxidase in peroxisomes of bovine kidney and liver: an immunocytochemical study.

Zaar

1996

J Histochem Cytochem.

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“…29) Other than the aforementioned study, to our knowledge, there have been no previous reports of the effects of the compounds listed in Table 2 on the activity of mammalian DDO. On the other hand, it was reported recently that the activity of DDO from the fungus Trichoderma harzianum is inhibited by several metals, including MgCl 2 , NiCl 2 and CuCl 2 (43%, 94% and 99% inhibition, respectively) 49) ; however, these metals had no significant effect on the activity of human DDO (Table 2).…”

Section: )mentioning

confidence: 90%

“…28,29,31) In addition, because aminooxyacetic acid was found to non-competitively inhibit DDO activity, binding of DDO to this compound was also examined. Malonate, mesotartrate and aminooxyacetic acid all inhibited the enzymatic activities of human, rat and mouse DDOs towards D-Asp in a dose-dependent manner, and the IC 50 values of these compounds were determined (data not shown).…”

Section: Characterization and Comparison Of The Kinetic Properties Ofmentioning

confidence: 99%

“…16,17) Overall, human DDO is an attractive therapeutic target and several compounds that inhibit the activity of mammalian DDO in vitro have been identified to date; however, the inhibitory potency of these compounds is limited. [28][29][30][31][32][33] Preclinical studies using experimental rodents are essential prerequisites for evaluating the in vivo effects of clinically useful enzyme inhibitors. However, species-related differences in some properties of target enzymes occur frequently and can lead to inaccurate evaluation of the in vivo effects of the inhibitors; therefore, it is vital to characterize and compare the properties of human enzymes with those of their rodent homologs.…”

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confidence: 99%

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Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes

Katane

Kawata

Nakayama

et al. 2015

Biological & Pharmaceutical Bulletin

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Human DDO is considered an attractive therapeutic target, and DDO inhibitors may be potential lead compounds for the development of new drugs against the aforementioned diseases. However, human DDO has not been characterized in detail and, although preclinical studies using experimental rodents are prerequisites for evaluating the in vivo effects of potential inhibitors, the existence of species-specific differences in the properties of human and rodent DDOs is still unclear. Here, the enzymatic activity and characteristics of purified recombinant human DDO were analyzed in detail. The kinetic and inhibitor-binding properties of this enzyme were also compared with those of purified recombinant rat and mouse DDOs. In addition, structural models of human, rat, and mouse DDOs were generated and compared. It was found that the differences among these DDO proteins occur in regions that appear involved in migration of the substrate/product in and out of the active site. In summary, detailed characterization of human DDO was performed and provides useful insights into the use of rats and mice as experimental models for evaluating the in vivo effects of DDO inhibitors. Alzheimer's disease, 9,10) and amyotrophic lateral sclerosis. Key words 11,12)Unlike the tissue-specific expression of D-Ser, substantial amounts of free D-Asp are present in a wide variety of mammalian tissues and cells, particularly those of the central nervous, neuroendocrine, and endocrine systems. Several lines of evidence suggest that D-Asp plays an important role in regulating developmental processes, hormone secretion, and steroidogenesis. [13][14][15] The amounts of D-Asp in human seminal plasma and spermatozoa are significantly lower in oligoasthenoteratospermic and azoospermic donors than normospermic donors. 16) Furthermore, in female patients undergoing in vitro fertilization, the D-Asp content of pre-ovulatory follicular fluid is lower in older patients than in younger patients; this decrease in D-Asp content appears to reflect a reduction in oocyte quality and fertilization competence. 17) Overall, current evidence suggests that decreases in D-Asp levels may be involved in the pathophysiology of infertility. Furthermore, D-Asp stimulates the NMDA receptor by acting as an agonist that binds to the L-Glu-binding site of the receptor. 18,19) Recent studies have suggested that, similar to D-Ser, D-Asp acts as a signaling molecule in nervous and neuroendocrine systems, at least in part, by binding to the NMDA receptor, and plays an important role in the regulation of brain functions. 14,15,20) In support of this proposal, it was reported recently that D-Asp levels in the prefrontal cortex and striatum of post-mortem brains of schizophrenic patients are significantly lower than those of non-psychiatrically ill individuals. 21) In mammalian tissues, two types of degradative enzymes that are stereospecific for D-amino acids have been identified, namely, D-amino acid oxidase (DAO, also abbreviated as DAAO; EC 1.4.3.3) and D-Asp oxidase (DDO, also ab...

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“…Although no conclusions can be drawn at this time, some physiological processes in which this reaction may be involved include the production of oxalate, the release of histamine caused by cysteamine (44)(45)(46), the effects (48) of nicotinic acid on metabolism, and an important step in brain metabolism [kidney D-AA oxidase, which is identical to the brain enzyme (49), is inhibited by tranquilizers (50,51)]. Some other enzymes closely related to D-AA oxidase, which may also be catalyzing a reaction involving glyoxylate, include D-aspartate oxidase (52) and L-a-hydroxy acid oxidase (53).…”

mentioning

confidence: 99%

Reactions of cysteamine and other amine metabolites with glyoxylate and oxygen catalyzed by mammalian D-amino acid oxidase.

Hamilton¹,

Buckthal²,

Mortensen³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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, and Lcysteine ethyl ester. Notable physiological amines that do not support a rapid 02 reaction under the above conditions include histamine, serotonin, epinephrine, norepinephrine, spermidine, spermine, and cadaverine. A more detailed kinetic investigation of the reactions involving the first four reactive amines listed above indicated that the cysteamine reaction proceeds at a rapid rate even when cysteamine and glyoxylate are present at less than millimolar concentrations, but greater than millimolar concentrations are needed in the other amine reactions in order to observe a reasonable rate. At low concentrations and pH 7.4, the cysteamine-glyoxylate substrate (presumably thiazolidine-2-carboxylic acid) reacts an order of magnitude faster than any other known D-amino acid oxidase substrate. Considerable circumstantial evidence suggests that the reaction involving cysteamine is occurring physiologically, but the reactions of other amines would be occurring in the cell at a very low rate, if at all. It is proposed that the product of the enzymic reaction may be a metabolic effector that can modify the reactivity of proteins or nucleic acids by covalent attachment. Although the presence of D-amino acid oxidase [D-aminoacid:oxygen oxidoreductase (deaminating), EC 1.4.3.3; D-AA oxidase] activity in mammalian tissues has been known (1, 2) since the early 1930s, the physiological function of the enzyme has remained unknown. The specific reaction catalyzed (3) by the oxidase is the transhydrogenation shown in Eq. I.

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d-aspartate oxidase of kidney

Cited by 53 publications

References 11 publications

Light and electron microscopic localization of D-aspartate oxidase in peroxisomes of bovine kidney and liver: an immunocytochemical study.

Light and electron microscopic localization of D-aspartate oxidase in peroxisomes of bovine kidney and liver: an immunocytochemical study.

Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes

Reactions of cysteamine and other amine metabolites with glyoxylate and oxygen catalyzed by mammalian D-amino acid oxidase.

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