d-Aspartate—An important bioactive substance in mammals: A review from an analytical and biological point of view

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

“…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 abbreviated as DASPO; EC 1.4.3.1).…”

“…Total RNA was extracted from the cells using the RNeasy Mini Kit (Qiagen, Hilden, Germany), according to the manufacturer's instructions. For first-strand cDNA synthesis, the RNA samples (5 µg) were reverse-transcribed in a 20 µL reaction mixture containing 200 units of SuperScript III Reverse Transcriptase and 0.5 µg of oligo(dT) [12][13][14][15][16][17][18] primer (Invitrogen, Carlsbad, CA, U.S.A.). After incubation at 50°C for 1 h, 1 µL (2 units) of RNaseH (Invitrogen) was added and the mixture was incubated at 37°C for 20 min.…”

“…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.…”

“…As described above, reduced levels of D-Asp in the nervous system and a resulting dysfunction in NMDA receptor-mediated neurotransmission is thought to occur during the onset of various mental disorders, including schizophrenia 14,15,20,21) ; hence, a substance capable of increasing D-Asp levels and activating NMDA receptor function may present a novel foundation for the development of antipsychotic drugs. One way to increase the level of D-Asp is to prevent its metabolic degradation by DDO.…”

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

“…Several lines of evidence suggest that D-serine plays an important role in the regulation of brain functions by acting as co-agonist for the NMDA receptor and perturbations in D-serine in the nervous system have recently been implicated in the pathophysiology of various neuropsychiatric disorders (see Katane et al, 2015 for references). Recent studies have also shown that D-aspartate acts as signaling molecule in nervous and neuroendocrine systems at least in part by binding to the NMDA receptor and, thus plays an important role in the regulation of brain function (Katane and Homma, 2011;Errico et al, 2012;Ota et al, 2012). Furthermore, peroxisomes, at least in humans, are the sole site of L-pipecolic acid oxidase activity which is a metabolite derived from lysine (Wanders et al, 1988;Mihalik et al, 1989).…”