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Molecular Plant Jan 2010Plants are either directly or indirectly the source of most of the essential amino acids in animal diets. Four of these essential amino acids-methionine, threonine,... (Review)
Review
Plants are either directly or indirectly the source of most of the essential amino acids in animal diets. Four of these essential amino acids-methionine, threonine, isoleucine, and lysine-are all produced from aspartate via a well studied biosynthesis pathway. Given the nutritional interest in essential amino acids, the aspartate-derived amino acid pathway has been the subject of extensive research. Additionally, several pathway enzymes serve as targets for economically important herbicides, and some of the downstream products are biosynthetic precursors for other essential plant metabolites such as ethylene and S-adenosylmethionine. Recent and ongoing research on the aspartate-derived family of amino acids has identified new enzyme activities, regulatory mechanisms, and in vivo metabolic functions. Together, these discoveries will open up new possibilities for plant metabolic engineering.
Topics: Amino Acids; Arabidopsis; Aspartic Acid; Models, Biological; Plants
PubMed: 20019093
DOI: 10.1093/mp/ssp104 -
Journal of the American Chemical Society Mar 2017O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. It...
O-Linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide. Aspartate-to-isoaspartate isomerization in proteins occurs in cells but was previously thought to be exclusively non-enzymatic. Our findings suggest it may also be enzyme-catalyzed. In addition to OGT, enzymes that may catalyze aspartate to isoaspartate isomerization include PARPs, enzymes known to ribosylate aspartate residues in the process of poly(ADP-ribosyl)ation.
Topics: Aspartic Acid; Biocatalysis; Glycosylation; Host Cell Factor C1; Humans; Molecular Conformation; N-Acetylglucosaminyltransferases
PubMed: 28207246
DOI: 10.1021/jacs.6b12866 -
Reproductive Biology Mar 2022D-Aspartate (D-Asp) and its methylated form N-methyl-d-aspartate (NMDA) promote spermatogenesis by stimulating the biosynthesis of sex steroid hormones. d-Asp also...
D-Aspartate (D-Asp) and its methylated form N-methyl-d-aspartate (NMDA) promote spermatogenesis by stimulating the biosynthesis of sex steroid hormones. d-Asp also induces spermatogonia proliferation directly by activating the ERK/Aurora B pathway. In the present study, a mouse spermatocyte-derived cell line (GC-2) which represents a stage between preleptotene spermatocyte and round spermatids was exposed to 200 μM d-Asp or 50 μM NMDA for 30 min, 2 h, and 4 h to explore the influence of these amino acids on cell proliferation and mitochondrial activities occurring during this process. By Western blotting analyses, the expressions of AMPAR (GluA1-GluA2/3 subunits), cell proliferation as well as mitochondria functionality markers were determined at different incubation times. The results revealed that d-Asp or NMDA stimulate proliferation and meiosis in the GC-2 cells via the AMPAR/ERK/Akt pathway, which led to increased levels of the PCNA, p-H3, and SYCP3 proteins. The effects of d-Asp and NMDA on the mitochondrial functionality of the GC-2 cells strongly suggested an active role of these amino acids in germ cell maturation. In both d-Asp- and NMDA-treated GC-2 cells mitochondrial biogenesis as well as mitochondrial fusion are increased while mitochondria fission is inhibited. Finally, the findings showed that NMDA significantly increased the expressions of the CII, CIII, CIV, and CV complexes of oxidative phosphorylation system (OXPHOS), whereas d-Asp induced a significant increase in the expressions only of the CIV and CV complexes. The present study provides novel insights into the mechanisms underlying the role of d-Asp and NMDA in promoting spermatogenesis.
Topics: Animals; D-Aspartic Acid; Male; Mice; N-Methylaspartate; Spermatocytes; Spermatogenesis; Spermatogonia
PubMed: 35032869
DOI: 10.1016/j.repbio.2021.100601 -
Journal of Neurochemistry Aug 2000N-Acetyl-L-aspartate (NAA) and its derivative N-acetylaspartylglutamate (NAAG) are major osmolytes present in the vertebrate brain. Although they are synthesized... (Review)
Review
N-Acetyl-L-aspartate (NAA) and its derivative N-acetylaspartylglutamate (NAAG) are major osmolytes present in the vertebrate brain. Although they are synthesized primarily in neurons, their function in these cells is unclear. In the brain, these substances undergo intercompartmental cycles in which they are released by neurons in a regulated fashion and are then rapidly hydrolyzed by catabolic enzymes associated with glial cells. Recently, the catabolic enzyme for NAA hydrolysis has been found to be expressed only in oligodendrocytes, and the catabolic enzyme for NAAG expressed only in astrocytes. These results indicate an unusual tricellular metabolic sequence for the synthesis and hydrolysis of NAAG wherein it is synthesized in neurons from NAA and L-glutamate, hydrolyzed to NAA and L-glutamate by astrocytes, and further hydrolyzed to L-aspartate and acetate by oligodendrocytes. Since the discovery that the NAA and NAAG anabolic products of neurons are specifically targeted to oligodendrocytes and astrocytes, respectively, this unique metabolic compartmentalization also suggests that these substances may play an important role in cell-specific glial signaling. In this review, it is hypothesized that a key function of NAA and NAAG in the vertebrate brain is in cell signaling and that these substances are important in the regulation of interactions of brain cells and in the establishment and maintenance of the nervous system.
Topics: Animals; Aspartic Acid; Brain; Dipeptides; Humans; Neuroglia; Neurons; Neurotransmitter Agents; Signal Transduction; Vertebrates
PubMed: 10899919
DOI: 10.1046/j.1471-4159.2000.0750453.x -
British Journal of Pharmacology Apr 19881. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro...
1. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro and in vivo was studied. 2. Neither quinolinic acid nor NMDLA had any effect on the basal or potassium-evoked release of [3H]-D-aspartate from slices of rat cerebral cortex either in the presence or absence of magnesium. Kainic acid failed to modify the basal efflux of [3H]-D-aspartate but significantly inhibited (by 34.4% +/- 0.04%, P less than 0.05) the potassium-evoked release. 3. Neither quinolinate nor NMDLA had any effect on the basal efflux of endogenous amino acids from rat cortical slices either in the presence or absence of magnesium ions at concentrations between 10 microM and 5 mM. 4. Both NMDLA (1 mM) and quinolinate (5 mM) produced an efflux of endogenous aspartate (371.4% +/- 11.6%; 389.3% +/- 12.1%) and glutamate (405.4% +/- 13.6%; 430.1 +/- 8.7%) respectively from the rat cerebral cortex in vivo (P less than 0.01). The quinolinic acid-evoked efflux was abolished by the NMDLA antagonist, 2-amino-5-phosphonovaleric acid (200 microM). 5. Kainic acid also caused an efflux of endogenous amino acids from the rat cerebral cortex in vivo. However, the profile of this release was different from that produced by quinolinate and NMDLA. 6. The results add further support to the suggestion that quinolinic acid acts at the NMDLA-preferring receptor and may also explain the requirement for intact afferent projections for the neurotoxic effects of quinolinate to be manifested.
Topics: 2-Amino-5-phosphonovalerate; Amino Acids; Animals; Anticonvulsants; Aspartic Acid; Cerebral Cortex; In Vitro Techniques; Kainic Acid; Male; N-Methylaspartate; Pyridines; Quinolinic Acid; Quinolinic Acids; Rats; Rats, Inbred Strains; Valine
PubMed: 2898959
DOI: 10.1111/j.1476-5381.1988.tb11474.x -
The Journal of Physiology Apr 1985Neurones from the ventral half of mouse embryo spinal cord were grown in dissociated culture and voltage clamped. The current-voltage relation of responses evoked by...
Neurones from the ventral half of mouse embryo spinal cord were grown in dissociated culture and voltage clamped. The current-voltage relation of responses evoked by N-methyl-D-aspartic acid (NMDA), L-glutamic acid and kainic acid was recorded in media of different ionic composition. On removal of Mg2+ from the extracellular solution, responses to NMDA and L-glutamate became less voltage sensitive, such that NMDA responses were no longer associated with a region of negative slope conductance. The antagonism of NMDA responses produced by application of Mg2+ to neurones bathed in nominally Mg2+-free solutions shows voltage dependence and uncompetitive kinetics. Voltage-jump experiments showed that the voltage-dependent action of Mg2+ occurred rapidly, and with complex kinetics. Ni2+ and Cd2+, two potent blockers of calcium currents in spinal cord neurones, had significantly different potencies as NMDA antagonists, Ni2+ being of greater potency than Mg2+, and Cd2+ considerably weaker. The voltage-dependent block of NMDA responses produced by physiological concentrations of Mg2+ is sufficient to explain the apparent increase in membrane resistance produced by NMDA in current-clamp experiments, and the ability of NMDA to support repetitive firing. Substitution of choline for Na+ produced a hyperpolarizing shift in the reversal potential for responses evoked by kainic acid consistent with an increase in permeability to Na+ and K+. In choline-substituted solutions, the reversal potential of NMDA responses was more positive than that recorded for kainic acid, and in addition NMDA responses showed enhanced desensitization.
Topics: Action Potentials; Animals; Aspartic Acid; Cells, Cultured; Glutamates; Glutamic Acid; Ion Channels; Kainic Acid; Magnesium; Membrane Potentials; Mice; N-Methylaspartate; Neurons; Spinal Cord; Time Factors
PubMed: 2580984
DOI: 10.1113/jphysiol.1985.sp015633 -
International Journal of Pharmaceutics Jan 2017A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was...
A series of 14 cationic derivatives of poly(aspartic acid) i.e. cationic polyaspartamides with different (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups was synthesized by nucleophilic addition on polysuccinimide. The resulting polyaspartamides have moderate amphiphilic properties. Relationships between the structure and ratio of side groups and in vitro properties of polyaspartamides, including their cytotoxic and membrane-damaging activity towards human cell lines, primary skin fibroblasts and erythrocytes, were established and discussed. Cationic polyaspartamides vary in their DNA-binding, condensing and nuclease-protecting characteristics depending on the concentration ratio of (dialkylamino)alkyl and alkyl or hydroxyalkyl side groups. Effective cell transfection was achieved upon polyaspartamide-mediated plasmid DNA delivery in serum-free medium in the presence of chloroquine. Effect of serum proteins adsorption onto polyaspartamide based polyplexes, and the role of concentration of polyplexes in culture medium in their colloidal stability and transfection process were demonstrated. Synthesized polyaspartamides are biocompatible and long-acting gene carriers, which are applied to cells after dilution and without washing, thus providing transfection level comparable to that of commercial transfection reagent.
Topics: Adsorption; Amides; Aspartic Acid; Blood Proteins; Cell Membrane; Cell Survival; Cells, Cultured; DNA; Drug Carriers; Erythrocytes; Fibroblasts; Humans; Peptides; Primary Cell Culture; Structure-Activity Relationship; Transfection
PubMed: 27931785
DOI: 10.1016/j.ijpharm.2016.12.007 -
Magnetic Resonance in Medicine Jul 2016To investigate a novel Hadamard-encoded spectral editing scheme and evaluate its performance in simultaneously quantifying N-acetyl aspartate (NAA) and N-acetyl aspartyl...
PURPOSE
To investigate a novel Hadamard-encoded spectral editing scheme and evaluate its performance in simultaneously quantifying N-acetyl aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG) at 3 Tesla.
METHODS
Editing pulses applied according to a Hadamard encoding scheme allow the simultaneous acquisition of multiple metabolites. The method, called HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy), was optimized to detect NAA and NAAG simultaneously using density-matrix simulations and validated in phantoms at 3T. In vivo data were acquired in the centrum semiovale of 12 normal subjects. The NAA:NAAG concentration ratio was determined by modeling in vivo data using simulated basis functions. Simulations were also performed for potentially coedited molecules with signals within the detected NAA/NAAG region.
RESULTS
Simulations and phantom experiments show excellent segregation of NAA and NAAG signals into the intended spectra, with minimal crosstalk. Multiplet patterns show good agreement between simulations and phantom and in vivo data. In vivo measurements show that the relative peak intensities of the NAA and NAAG spectra are consistent with a NAA:NAAG concentration ratio of 4.22:1 in good agreement with literature. Simulations indicate some coediting of aspartate and glutathione near the detected region (editing efficiency: 4.5% and 78.2%, respectively, for the NAAG reconstruction and 5.1% and 19.5%, respectively, for the NAA reconstruction).
CONCLUSION
The simultaneous and separable detection of two otherwise overlapping metabolites using HERMES is possible at 3T. Magn Reson Med 76:11-19, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Adult; Algorithms; Aspartic Acid; Brain; Dipeptides; Female; Humans; Male; Molecular Imaging; Phantoms, Imaging; Proton Magnetic Resonance Spectroscopy; Reproducibility of Results; Sensitivity and Specificity
PubMed: 27089868
DOI: 10.1002/mrm.26233 -
Psychiatry Research Aug 2013Over the past two decades, many magnetic resonance spectroscopy (MRS) studies reported lower N-acetylaspartate (NAA) in key brain regions of patients with schizophrenia... (Meta-Analysis)
Meta-Analysis Review
Over the past two decades, many magnetic resonance spectroscopy (MRS) studies reported lower N-acetylaspartate (NAA) in key brain regions of patients with schizophrenia (SZ) compared to healthy subjects. A smaller number of studies report no difference in NAA. Many sources of variance may contribute to these discordant results including heterogeneity of the SZ subject populations and methodological differences such as MRS acquisition parameters, and post-acquisition analytic methods. The current study reviewed proton MRS literature reporting measurements of NAA in SZ with a focus on methodology. Studies which reported lower NAA were significantly more likely to have used longer echo times (TEs), while studies with shorter TEs reported no concentration difference. This suggests that NAA quantitation using MRS was affected by the choice of TE, and that published MRS literature reporting NAA in SZ using a long TE is confounded by apparent differential T2 relaxation effects between SZ and healthy control groups. Future MRS studies should measure T2 relaxation times. This would allow for spectral concentration measurements to be appropriately corrected for these relaxation effects. In addition, as metabolite concentration and T2 relaxation times are completely independent variables, this could offer distinct information about the metabolite of interest.
Topics: Aspartic Acid; Brain; Humans; Magnetic Resonance Spectroscopy; Reproducibility of Results; Schizophrenia
PubMed: 23769421
DOI: 10.1016/j.pscychresns.2013.03.005 -
FEBS Letters Sep 2003Probes for the occurrence of endogenous D-aspartic acid (D-Asp) and N-methyl-D-aspartic acid (NMDA) in the neural complex and gonads of a protochordate, the ascidian...
Probes for the occurrence of endogenous D-aspartic acid (D-Asp) and N-methyl-D-aspartic acid (NMDA) in the neural complex and gonads of a protochordate, the ascidian Ciona intestinalis, have confirmed the presence of these two excitatory amino acids and their involvement in hormonal activity. A hormonal pathway similar to that which occurs in vertebrates has been discovered. In the cerebral ganglion D-Asp is synthesized from L-Asp by an aspartate racemase. Then, D-Asp is transferred through the blood stream into the neural gland where it gives rise to NMDA by means of an NMDA synthase. NMDA, in turn, passes from the neuronal gland into the gonads where it induces the synthesis and release of a gonadotropin-releasing hormone (GnRH). The GnRH in turn modulates the release and synthesis of testosterone and progesterone in the gonads, which are implicated in reproduction.
Topics: Animals; Aspartic Acid; Ciona intestinalis; Female; Gonadotropin-Releasing Hormone; Gonads; In Vitro Techniques; Invertebrate Hormones; Male; N-Methylaspartate; Neurosecretory Systems; Progesterone; Reproduction; Stereoisomerism; Testosterone
PubMed: 14527686
DOI: 10.1016/s0014-5793(03)00921-9