Application | Comment | Organism |
---|---|---|
drug development | a DDO inhibitor that augments brain D-Asp levels can be a potent antipsychotic drug for the treatment of NMDA receptor-related disease | Mus musculus |
drug development | a DDO inhibitor that augments brain D-Asp levels can be a potent antipsychotic drug for the treatment of NMDA receptor-related disease | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
- |
Vanrija humicola |
from brain, expressed in Escherichia coli | Homo sapiens |
from kidney, expressed in Escherichia coli | Mus musculus |
from kidney, expressed in Escherichia coli | Sus scrofa |
from kidney, expressed in Escherichia coli | Bos taurus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | intense D-Asp immunoreactivity is observed in the intermediate lobe of the pituitary gland of the DDO-deficient mice, phenotype of DDO-deficient mice, detailed overview | Mus musculus |
R216X | activities of mouse DDO against acidic D-amino acids are virtually extinguished or significantly reduced by replacements of the Arg216 residue with other amino acid residues | Mus musculus |
R237X | activities of mouse DDO against acidic D-amino acids are virtually extinguished or significantly reduced by replacements of the Arg237 residue with other amino acid residues | Mus musculus |
S308G | the mutation results in lack of a side-chain OH group at position 308, and increases mutant enzyme catalytic efficiency against D-Asp and NMDA to about 7-10times higher than that of the wild-type enzyme. Moreover, the dissociation-constant value for FAD of this Gly-substitution mutant is significantly lower than that of the wild-type enzyme, suggesting that it has enhanced ability to bind to FAD | Mus musculus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
malonate | - |
Bos taurus | |
malonate | - |
Caenorhabditis elegans | |
malonate | - |
Homo sapiens | |
malonate | - |
Mus musculus | |
malonate | - |
Ovis aries | |
malonate | - |
Rattus norvegicus | |
malonate | - |
Sus scrofa | |
malonate | - |
Vanrija humicola | |
meso-tartrate | - |
Bos taurus | |
meso-tartrate | - |
Caenorhabditis elegans | |
meso-tartrate | - |
Homo sapiens | |
meso-tartrate | - |
Mus musculus | |
meso-tartrate | - |
Ovis aries | |
meso-tartrate | - |
Rattus norvegicus | |
meso-tartrate | - |
Sus scrofa | |
meso-tartrate | - |
Vanrija humicola | |
thiolactomycin | - |
Bos taurus | |
thiolactomycin | - |
Caenorhabditis elegans | |
thiolactomycin | - |
Homo sapiens | |
thiolactomycin | - |
Mus musculus | |
thiolactomycin | - |
Ovis aries | |
thiolactomycin | - |
Rattus norvegicus | |
thiolactomycin | - |
Sus scrofa | |
thiolactomycin | - |
Vanrija humicola |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
axon | - |
Rattus norvegicus | 30424 | - |
cytoplasm | DDO-2 | Caenorhabditis elegans | 5737 | - |
extracellular | DDO-3 | Caenorhabditis elegans | - |
- |
heterochromatin | in magnocellular neurons of the rat supraoptic nucleus, but not in other subcellular structures of the nucleus and soma, including the nucleoplasm and cytoplasm | Rattus norvegicus | 792 | - |
nucleolus | in magnocellular neurons of the rat supraoptic nucleus | Rattus norvegicus | 5730 | - |
peroxisome | - |
Mus musculus | 5777 | - |
peroxisome | - |
Homo sapiens | 5777 | - |
peroxisome | - |
Rattus norvegicus | 5777 | - |
peroxisome | - |
Sus scrofa | 5777 | - |
peroxisome | - |
Bos taurus | 5777 | - |
peroxisome | - |
Ovis aries | 5777 | - |
peroxisome | DDO-1 | Caenorhabditis elegans | 5777 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
D-aspartate + H2O + O2 | Mus musculus | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Homo sapiens | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Rattus norvegicus | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Sus scrofa | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Bos taurus | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Ovis aries | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Caenorhabditis elegans | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | Vanrija humicola | - |
oxaloacetate + NH3 + H2O2 | - |
? | |
D-glutamate + H2O + O2 | Caenorhabditis elegans | preferred substrate. It is possible that excess amounts of D-Glu are as toxic for Caenorhabditis elegans as they are for the silkworm, and that Caenorhabditis elegans needs DDOs to deaminate D-Glu and thereby neutralize the toxicity of diet-derived D-Glu | 2-oxoglutarate + NH3 + H2O2 | - |
? | |
additional information | Caenorhabditis elegans | H2O2 that is generated in the enzymatic reaction catalyzed by Caenorhabditis elegans DDO-1 and DDO-2 is conceivably degraded by catalase colocalized with each DDO | ? | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Mus musculus | - |
oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Homo sapiens | - |
oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Rattus norvegicus | - |
oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Sus scrofa | - |
oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Bos taurus | - |
oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Ovis aries | - |
oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | Caenorhabditis elegans | - |
oxaloacetate + methylamine + H2O2 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Bos taurus | - |
- |
- |
Caenorhabditis elegans | - |
at least three genes encoding functional DDO isozymes DDO-1, DDO-2, and DDO-3 | - |
Homo sapiens | - |
- |
- |
Mus musculus | - |
- |
- |
Ovis aries | - |
- |
- |
Rattus norvegicus | - |
- |
- |
Sus scrofa | - |
- |
- |
Vanrija humicola | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme | Vanrija humicola |
recombinant enzyme from Escherichia coli | Mus musculus |
recombinant enzyme from Escherichia coli | Homo sapiens |
recombinant enzyme from Escherichia coli | Sus scrofa |
recombinant enzyme from Escherichia coli | Bos taurus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
adrenal gland | - |
Rattus norvegicus | - |
adrenal gland | adrenal cortex and adrenal medulla epinephrine cells | Mus musculus | - |
brain | cerebellar cortex Bergmann glia | Mus musculus | - |
brain | embryonic, D-Asp initially emerges in the hindbrain and then spreads into the forebrain. Within nerve cells of the rat embryonic brain, D-Asp first occurs in the cell bodies of neuroblasts in the outer layer of the neuronal epithelium, and then it appears in the processes of the cells | Rattus norvegicus | - |
cerebral cortex | relatively high enzyme expression just after birth, the content gradually decreases thereafter | Homo sapiens | - |
cerebrum | relatively high enzyme expression just after birth, the content gradually decreases thereafter | Rattus norvegicus | - |
follicular fluid | - |
Homo sapiens | - |
gastric juice | - |
Homo sapiens | - |
hippocampus | - |
Mus musculus | - |
hypothalamus | in the cell bodies of the neurons | Rattus norvegicus | - |
kidney | - |
Rattus norvegicus | - |
kidney | - |
Sus scrofa | - |
kidney | - |
Bos taurus | - |
kidney | - |
Ovis aries | - |
kidney | in Bowman's capsule, renal thin limbs of Henle's loop | Mus musculus | - |
Leydig cell | - |
Mus musculus | - |
liver | - |
Mus musculus | - |
liver | - |
Homo sapiens | - |
liver | - |
Rattus norvegicus | - |
additional information | development-related patterns of D-Asp expression differ among various mammalian tissues, overview | Mus musculus | - |
additional information | development-related patterns of D-Asp expression differ among various mammalian tissues, overview | Homo sapiens | - |
additional information | development-related patterns of D-Asp expression differ among various mammalian tissues, overview | Rattus norvegicus | - |
additional information | development-related patterns of D-Asp expression differ among various mammalian tissues, overview | Sus scrofa | - |
additional information | development-related patterns of D-Asp expression differ among various mammalian tissues, overview | Bos taurus | - |
additional information | development-related patterns of D-Asp expression differ among various mammalian tissues, overview | Ovis aries | - |
neuron | primary cultured | Rattus norvegicus | - |
pancreas | - |
Rattus norvegicus | - |
PC-12 cell | pheochromocytoma cells | Rattus norvegicus | - |
pineal gland | D-Asp content in the adult rat pineal gland is very high, especially in the distal (caudal) region of the gland, little staining is found in the proximal (rostral) region | Rattus norvegicus | - |
pinealocyte | - |
Rattus norvegicus | - |
pituitary gland | intermediate lobe | Mus musculus | - |
pituitary gland | prolactin-producing cells in the anterior lobe and microglial cells in the posterior lobe, D-Asp immunoreactivity is observed specifically in prolactin-producing mammotrophs or in a closely related cell type | Rattus norvegicus | - |
retina | - |
Mus musculus | - |
retina | - |
Rattus norvegicus | - |
salivary gland | - |
Homo sapiens | - |
salivary gland | - |
Rattus norvegicus | - |
spermatozoon | - |
Homo sapiens | - |
testis | - |
Mus musculus | - |
testis | - |
Rattus norvegicus | - |
testis | - |
Sus scrofa | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
D-aspartate + H2O + O2 | - |
Mus musculus | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Homo sapiens | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Rattus norvegicus | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Sus scrofa | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Bos taurus | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Ovis aries | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Caenorhabditis elegans | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | - |
Vanrija humicola | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Mus musculus | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Homo sapiens | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Rattus norvegicus | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Sus scrofa | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Bos taurus | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Ovis aries | oxaloacetate + NH3 + H2O2 | - |
? | |
D-aspartate + H2O + O2 | in the first step of the reaction, which is the only enzymatic step of the whole reaction scheme, DDO catalyzes the dehydrogenation of a D-amino acid to generate the corresponding imino acid, coupled with the reduction of FAD. Subsequently, FAD reoxidizes spontaneously in the presence of O2, producing H2O2, while the imino acid nonenzymatically hydrolyzes to 2-oxo acid and NH3 | Caenorhabditis elegans | oxaloacetate + NH3 + H2O2 | - |
? | |
D-glutamate + H2O + O2 | preferred substrate | Caenorhabditis elegans | 2-oxoglutarate + NH3 + H2O2 | - |
? | |
D-glutamate + H2O + O2 | preferred substrate. It is possible that excess amounts of D-Glu are as toxic for Caenorhabditis elegans as they are for the silkworm, and that Caenorhabditis elegans needs DDOs to deaminate D-Glu and thereby neutralize the toxicity of diet-derived D-Glu | Caenorhabditis elegans | 2-oxoglutarate + NH3 + H2O2 | - |
? | |
additional information | H2O2 that is generated in the enzymatic reaction catalyzed by Caenorhabditis elegans DDO-1 and DDO-2 is conceivably degraded by catalase colocalized with each DDO | Caenorhabditis elegans | ? | - |
? | |
additional information | Arg216, Tyr223, Arg237, Arg278, and Ser308 residues of DDO are presumed to be important in catalytic activity and substrate binding | Sus scrofa | ? | - |
? | |
additional information | Arg216, Tyr223, Arg237, Arg278, and Ser308 residues of DDO are presumed to be important in catalytic activity and substrate binding, overview | Mus musculus | ? | - |
? | |
additional information | in contrast to the mammalian and Cryptococcus humicola DDOs, the three kinds of Caenorhabditis elegans DDOs show relatively higher catalytic efficiency against D-Glu than against D-Asp and NMDA | Caenorhabditis elegans | ? | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Mus musculus | oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Homo sapiens | oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Rattus norvegicus | oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Sus scrofa | oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Bos taurus | oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Ovis aries | oxaloacetate + methylamine + H2O2 | - |
? | |
N-methyl-D-aspartate + H2O + O2 | - |
Caenorhabditis elegans | oxaloacetate + methylamine + H2O2 | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 37000-38000 | Mus musculus |
? | x * 37000-38000 | Homo sapiens |
? | x * 37000-38000 | Rattus norvegicus |
homotetramer | 4 * 37000-38000 | Sus scrofa |
homotetramer | 4 * 37000-38000 | Vanrija humicola |
monomer | 1 * 37000-38000 | Bos taurus |
More | three-dimensional structure by homology-modeling | Mus musculus |
More | three-dimensional structure by homology-modeling | Sus scrofa |
Synonyms | Comment | Organism |
---|---|---|
DDO | - |
Mus musculus |
DDO | - |
Homo sapiens |
DDO | - |
Rattus norvegicus |
DDO | - |
Sus scrofa |
DDO | - |
Bos taurus |
DDO | - |
Ovis aries |
DDO | - |
Caenorhabditis elegans |
DDO | - |
Vanrija humicola |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO | Ovis aries | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO | Caenorhabditis elegans | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO, the enzyme contains a FAD-binding consensus sequence Gly-X-Gly-X-X-Gly | Mus musculus | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO, the enzyme contains a FAD-binding consensus sequence Gly-X-Gly-X-X-Gly | Homo sapiens | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO, the enzyme contains a FAD-binding consensus sequence Gly-X-Gly-X-X-Gly | Rattus norvegicus | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO, the enzyme contains a FAD-binding consensus sequence Gly-X-Gly-X-X-Gly | Sus scrofa | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO, the enzyme contains a FAD-binding consensus sequence Gly-X-Gly-X-X-Gly | Bos taurus | |
FAD | one molecule of FAD is noncovalently bound to one molecule of DDO, the enzyme contains a FAD-binding consensus sequence Gly-X-Gly-X-X-Gly | Vanrija humicola |
General Information | Comment | Organism |
---|---|---|
additional information | melatonin secretion and D-Asp release from pinealocytes are enhanced by stimulation with noradrenaline, after which the melatonin secretion is suppressed by the action of the released D-Asp on the cells. Through this negative feedback mechanism, noradrenaline may regulate its ability to induce melatonin secretion in the pineal gland | Rattus norvegicus |
physiological function | D-Asp is important in the development and neurogenesis of the brain. D-Asp plays a regulatory role in the synthesis and secretion of prolactin in the anterior lobe of the pituitary gland. D-Asp directly interacts with DNA and/or acts on nuclear protein(s) involved in the regulation of gene transcription, through which d-Asp controls gene expression in the hypothalamo-neurohypophyseal system | Rattus norvegicus |
physiological function | relevance of D-Asp and DDO to NMDA receptor-related disease, D-Asp protects against sensorimotor-gating deficits, which are observed in schizophrenic patients, overview. D-Asp is important in the development and neurogenesis of the brain | Homo sapiens |
physiological function | relevance of D-Asp and DDO to NMDA receptor-related disease, overview. Phenotype of DDO-deficient mice, DDO-deficient mice display significant deficits in prepulse inhibition, and exhibit reduced immobility time in the Porsolt forced-swim test, a model of depression, suggesting that the genetic ablation of DDO has a specific antidepressant action, overview | Mus musculus |