Disease relevance of L-aspartic acid

• This peptide prevented neuronal cell death associated with the envelope protein (GP 120) from HIV, with excitotoxicity (N-methyl d-aspartate), with the beta amyloid peptide (putative cytotoxin in Alzheimer's disease), and with tetrodotoxin (electrical blockade) [1].
• Rat pheochromocytoma PC12 cells contain an appreciable amount of D-aspartate (257 +/- 31 pmol/10(7) cells) [2].
• d-Aspartate ligase has remained the last unidentified peptide bond-forming enzyme in the peptidoglycan assembly pathway of Gram-positive bacteria [3].
• In addition, these binding sites on lung cancer cells appear to be distinct from the N-methyl D-aspartate/PCP receptor ionophore complex reported to be present in rat brain [4].
• D-aspartate content of erythrocyte membrane proteins is decreased in uremia: implications for the repair of damaged proteins [5].

Psychiatry related information on L-aspartic acid

• Since the periods of maximal emergence of D-aspartate in the brain and periphery occur during critical periods of morphological and functional maturation of the organs, D-aspartate could participate in the regulation of these regulation of these developmental processes of the organs [6].
• Glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene as a positional candidate for attention-deficit/hyperactivity disorder in the 16p13 region [7].
• Therapeutic efficacy of N-methyl D-aspartate antagonist amantadine in febrile catatonia [8].
• Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia [9].
• These data suggest that decreased levels of D-aspartate could contribute to a lower NMDA receptor function and consequently contribute to the memory deficits seen in AD [10].

High impact information on L-aspartic acid

• The NMDA (N-methyl D-aspartate) receptors in the brain play a critical role in synaptic plasticity, synaptogenesis and excitotoxicity [11].
• The rate constant for D-aspartate formation in the brain is equal to the predicted value calculated for 37 degrees C. Accumulation of the uncommon D-aspartate isomer in myelinated white matter implies that there is little or no turnover of this tissue, and this may have a bearing on dysfunction of the aging brain or on other diseases of myelin [12].
• Autoradiography demonstrated prominent retrograde labeling of olivocerebellar climbing fiber neurons after injection of tritiated D-aspartate into the rat cerebellar cortex or deep nuclei [13].
• Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14C were measured by gas chromatography and accelerator-mass spectrometry, respectively [14].
• Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon [14].

Chemical compound and disease context of L-aspartic acid

• Recent reports indicate the presence of D-aspartate and D-glutamate in aging brain, human breast tumors, core amyloid plaques and neurofibrillary tangles of Alzheimer's brain [15].
• L-Glutamate in the extracellular space regulates endogenous D-aspartate homeostasis in rat pheochromocytoma MPT1 cells [16].
• N-methyl D-aspartate receptor antagonists such as ketamine have been used increasingly in clinical studies in an effort to minimize acute postoperative pain and reduce opioid requirements [17].
• Effect of inhibitors of N-linked oligosaccharide processing on the high-affinity transport of D-aspartate by C6 glioma cells [18].
• D-Proline and D-aspartate spiked (at 10(-4) M and 10(-5) M concentrations, respectively) into complex biological matrices (rabbit serum and homogenate of Aplysia californica buccal ganglion) are detected without matrix interferences [19].

Biological context of L-aspartic acid

• Experiments with a range of acidic amino acid analogues indicated that the ligand selectivities of these two binding sites conformed to those of the N-methyl D-aspartate and quisqualate receptor classes defined electrophysiologically [20].
• Differences in the macroscopic kinetics of channels activated by concentration jumps of L-glutamate or D-aspartate were correlated with differences in uptake kinetics, indicating a close correspondence of channel gating to state transitions in the transporter cycle [21].
• Exocytosis of D-aspartate further supports the role(s) of D-aspartate as a chemical transmitter in neuroendocrine cells [2].
• The murine N-methyl D-aspartate receptor subunit NR2C (epsilon-3) is encoded by a unique gene composed of 12 translated and three 5'-untranslated exons that spread over approximately 20 kilobases of genomic sequence [22].
• Neither L-A beta HA nor DL-AP3 blocked PI hydrolysis stimulated by D-aspartate in hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)[23]

Anatomical context of L-aspartic acid

• D-aspartate oxidase, visualized by enzyme histochemistry, is concentrated in neurons of the hippocampus, cerebral cortex, and olfactory epithelium, as well as choroid plexus and ependyma [24].
• In rats 3-4 weeks old, we observe D-aspartate in septal nuclei and in a subset of stellate and basket cells of the cerebellum [24].
• In the brain we observe discrete neuronal localizations of D-aspartate, especially in the external plexiform layer of the olfactory bulb, hypothalamic supraoptic and paraventricular nuclei, the medial habenula, and certain brainstem nuclei [24].
• Mechanisms of H+ and Na+ changes induced by glutamate, kainate, and D-aspartate in rat hippocampal astrocytes [25].
• To study the localization and efficiency of glutamate/aspartate membrane transport in the vicinity of intact glutamatergic synapses, the avascular lamprey spinal cord was incubated with D-aspartate, a metabolically inert transporter substrate [26].

Associations of L-aspartic acid with other chemical compounds

• The exogenous D-aspartate was localized by immunocytochemistry after aldehyde fixation [26].
• The presence of an additional guanidinium group in the active site of the DAAO mutant allowed the binding (and thus the oxidation) of D-aspartate, but it was also responsible for a lower catalytic activity on D-alanine [27].
• Indirect immunofluorescence microscopy with specific antibodies against d-aspartate indicated that the amino acid is present within a particulate structure, which is co-localized with dopamine and chromogranin A, markers for secretory granules, but not with synaptophysin, a marker for synaptic-like microvesicles [2].
• Upon the addition of KCl, an appreciable amount of D-aspartate (about 40 pmol/10(7) cells at 10 min) was released from cultured cells on incubation in the presence of Ca(2+) in the medium [2].
• After sucrose density gradient centrifugation of the postnuclear particulate fraction, about 80% of the d-aspartate was recovered in the secretory granule fraction [2].

Gene context of L-aspartic acid

• Autophosphorylation-dependent targeting of calcium/ calmodulin-dependent protein kinase II by the NR2B subunit of the N-methyl- D-aspartate receptor [28].
• The glutamate receptor, ionotropic, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the NMDA receptor, resides in this region and a recent study has reported an association between this gene and ADHD [7].
• Recent studies have demonstrated that mice lacking protein L-isoaspartate (D-aspartate) O-methyltransferase (Pcmt1-/- mice) have alterations in the insulin-like growth factor-I (IGF-I) and insulin receptor pathways within the hippocampal formation as well as other brain regions [29].
• The protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) can initiate the repair of age-damaged aspartyl and asparaginyl residues of intracellular proteins [30].
• 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 [31].

Analytical, diagnostic and therapeutic context of L-aspartic acid

• Quantification of excitatory amino acid uptake at intact glutamatergic synapses by immunocytochemistry of exogenous D-aspartate [26].
• Using two specific and sensitive fluorometric/HPLC methods and a GC-MS method, alone and in combination with D-aspartate oxidase, we have demonstrated for the first time that N-methyl-D-aspartate (NMDA), in addition to D-aspartate (D-Asp), is endogenously present as a natural molecule in rat nervous system and endocrine glands [32].
• Saturation kinetics within the cerebral cortex disclosed that this change of 3H-glutamate was possibly due to an increase in the maximal number of N-methyl- D-aspartate binding sites, an interpretation that was corroborated by Western blot analysis of N-methyl- D-aspartate 2A subunits [33].
• BACKGROUND AND PURPOSE: Based on neuroprotective efficacy in animal models, we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies [34].
• However, dorsal rhizotomy, without damage to dorsal radicular or spinal blood vessels, depressed the uptake (by 22-29%) and the release (by 50%) of D-aspartate only in quadrants ipsilateral to the lesion [35].

References