Disease relevance of DDO

• A homogenous preparation of DDO-1 was obtained using an expression system in Escherichia coli [1].
• 2,4-Dinitrotoluene (2,4-DNT) and 2,6-DNT are priority pollutants, and 2,4-DNT dioxygenase of Burkholderia sp. strain DNT (DDO) catalyzes the initial oxidation of 2,4-DNT to form 4-methyl-5-nitrocatechol and nitrite but has significantly less activity on other dinitrotoluenes and nitrotoluenes (NT) [2].

High impact information on DDO

• DAAO catalyzes the oxidative deamination of D-amino acids, with the exception of D-aspartate and D-glutamate (which are oxidized by D-aspartate oxidase, DASPO) [3].
• D-Amino acids administered to animals are absorbed by the intestine and transported through the blood-stream to solid tissues where they are oxidized in vivo by D-amino acid oxidase and D-aspartate oxidase to produce the same compounds they do in vitro; i.e. NH3, H2O2, and the keto acid corresponding to the amino acid ingested [4].
• Bacterially expressed human d-aspartate oxidase was shown to interact with the human PTS1-binding protein, peroxin protein 5 (PEX5p) [5].
• The functionality of the C-terminus (Ser-Asn-Leu; SNL) of human d-aspartate oxidase, an enzyme proposed to have a role in the inactivation of synaptically released d-aspartate, as a peroxisome-targeting signal (PTS1) was investigated in vivo and in vitro [5].
• cDNA cloning and expression of the flavoprotein D-aspartate oxidase from bovine kidney cortex [6].

Chemical compound and disease context of DDO

• The degradation of both 2,3-DNT and 2,5-DNT were achieved for the first time (no detectable activity with the wild-type enzyme) using whole Escherichia coli TG1 cells expressing DDO variants DntAc I204L and I204Y (0.70 +/- 0.03 and 0.22 +/- 0.02 nmol/min/mg protein for 2,5-DNT transformation, respectively) [2].

Biological context of DDO

• 3. Neither enzyme exhibits genetic polymorphism in European populations, but a rare electrophoretic variant phenotype (DASOX 2-1) was identified which suggests that the DASOX locus is autosomal and independent of the DAMOX locus [7].
• Structural analysis of the DDO cDNAs and genomic DNA showed that DDO-1 and DDO-2 are produced by alternative splicing from a single gene [1].
• It is noteworthy, that introduction of a sole, additional, positively charged residue in the active site is sufficient to optimize the reactivity on acidic d-amino acids, giving rise to kinetic properties similar to those of d-aspartate oxidase [8].
• Hence, oxidation of 2,3-DNT, 2,4-DNT, 2,5-DNT, 2,6-DNT, 2NT, and 4NT were enhanced here by performing saturation mutagenesis on codon I204 of the alpha subunit (DntAc) of DDO and by using a membrane agar plate assay to detect catechol formation [2].
• The fact that such a diploma has existed first as a DDO and latterly as the MDO (Membership) for some 50 years is remarkable in view of the relative infancy of most dental specialties and the fact that the General Dental Council has instigated a specialist register in orthodontics as recently as 1998 [9].

Anatomical context of DDO

• Whereas between most positive neurons only gradual differences were observed, in the hypothalamic paraventricular nucleus, neurons with high enzyme content were found next to others with no labeling. cDNA cloning of D-aspartate oxidase corroborates an inherent targeting signal sequence for protein import into peroxisomes [10].
• Peroxisome-enriched subcellular fractions were used to investigate the properties of gastropod D-aspartate oxidase and D-amino acid oxidase activities [11].

Associations of DDO with chemical compounds

• 6. On the other hand, the administration of clofibrate or dehydroepiandrosterone to female mice decreased the D-aspartate oxidase activity [12].
• DDO DntAc variant I204L also transformed both 2,6-DNT and 2,4-DNT 2-fold faster than wild-type DDO (0.8 +/- 0.6 nmol/min/mg protein and 4.7 +/- 0.5 nmol/min/mg protein, respectively) [2].
• A DAO mutant, in which I215-N225 is substituted by R216-G220 of DDO, showed D-aspartate-oxidizing activity that wild-type DAO does not exhibit, together with a considerable decrease in activity toward D-alanine [13].
• Spectrophotometric assay of D-aspartate and D-glutamate using D-aspartate oxidase with malate dehydrogenase and glutamate dehydrogenase [14].
• This method is based on the detection by HPLC of methylamine (CH(3)NH(2)) which comes from the oxidation of NMDA by D-aspartate oxidase, an enzyme which specifically oxidizes NMDA, yielding CH(3)NH(2) as one of the oxidative products of the reaction [15].

Analytical, diagnostic and therapeutic context of DDO

• D-Aspartate oxidase (DDO) cDNAs were isolated from the human brain RNA using the RT-PCR method [1].
• 2. Oral administration of D-aspartate to the animals increased the hepatic D-aspartate oxidase activity 2-3 fold in both genders without any significant difference in the rate of the increase between the genders [12].

References