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At least 523 records · Page 29Linked to original sources
PubMed1991

Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey.

N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA (15 mg/kg BW) induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone (TRH; 6 micrograms/kg BW, iv) were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate (200 mg/wk) reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.

Animals↗
PubMed1979

Deamination of glumatic and aspartic acids by Geotrichum candidum.

Strains of Geotrichum candidum were isolated from the surface of a commercial sample of Limburger cheese and from raw milk. Growth of the isolates in an acidified tryptone-yeast extract medium was accompanied by a rise in the pH of the medium from 3.5 to above 7.0 Ammonia production, as indicated by Nesslerization, was associated with the deamination of glutamic and aspartic acids. The first reaction in the production of ammonia from glutamic acid, isomerization to beta-methylaspartic acid, required vitamin B12 and the second reaction, the deamination of beta-methylaspartic acid to mesaconic acid and ammonia, was dependent on magnesium and potassium. The conversion of aspartic acid to fumaric acid and ammonia required magnesium. These minerals were in sufficient amounts in the Limburger cheese for optimum deaminase activity.

Ammonia↗
PubMed1992

Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action.

Tetanus toxin (100 nM) when preincubated with guinea pig cerebrocortical synaptosomes for 45 min reduces the final extent of the KCl-evoked, Ca(2+)-dependent, glutamate transmitter release to 30% of non-intoxicated controls. Similarly, 100 nM Botulinum neurotoxins, types A and B, preincubated for 90 min inhibit release to 45-60% of non-intoxicated controls. The toxins preferentially attenuate a slow phase of KCl-evoked glutamate release which may be associated with synaptic vesicle mobilization. Tetanus toxin additionally inhibits the release of aspartate, gamma-aminobutyric acid and met-enkephalin from the same preparation. Since amino acids and neuropeptides are released by distinct mechanisms, this indicates that the toxin affects a step common to both exocytotic pathways. When Ba2+ (which does not interact with calmodulin) is substituted for Ca2+, the control KCl-evoked release of each transmitter is unaffected and tetanus toxin is still inhibitory. Taken together these results implicate a calmodulin-independent locus (or loci) of action common to small- and large-dense-core vesicles and associated with vesicle transport.

Amino Acids↗
PubMed1992

Release of endogenous norepinephrine from rat hypothalamus by stimulation of N-methyl-D-aspartic acid receptors.

Release of endogenous dopamine and norepinephrine (NE) from rat hypothalamic slices superfused with Mg(++)-free medium in the presence of nomifensine and tyrosine was measured by high-performance liquid chromatography coupled to an electrochemical detector. Superfusion with L-glutamic acid or N-methyl-D-aspartic acid elicited a concentration-dependent release of NE but not of dopamine. The release of NE was transient, returning toward basal values despite the continued presence of the amino acid. Superfusion with 20 mM K+ caused a release of NE that declined at a slower rate. Mg++, DL-2-amino-5-phosphonopentanoic acid and MK-801 (D-5-methyl-10,11,dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate), but not 6-cyano-7-nitroquinoxaline-2,3-dione, inhibited the L-glutamic acid-evoked release of NE. The release of NE by L-glutamic acid was virtually abolished by tetrodotoxin and by elimination of Ca++ from and inclusion of 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid in the superfusion medium. Repeated L-glutamic acid applications displayed a decreased response, whereas repeated exposure to 20 mM K+ did not. Exposure to L-glutamic acid in the absence of Ca++ (plus 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) or in the presence of DL-2-amino-5-phosphonopentanoic acid did not reduce the effects seen on subsequent exposure to L-glutamic acid. Exposure to L-glutamic acid in the absence of Mg++ reduced the effect of a subsequent exposure to L-glutamic acid. These observations provide evidence for an indirect modulation of rat hypothalamic endogenous NE by the N-methyl-D-aspartate receptor.

Animals↗
PubMed2005

Infrared and laser Raman spectral studies of bis(dl-aspartic acid) sulfate.

The infrared and Raman spectra of bis(dl-aspartic acid) sulfate in the crystalline state are recorded at room temperature and the vibrational assignments of the observed wavenumbers are made. The presence of two carbonyl (CO) groups has been identified in the title complex and the two carbonyl groups are in different environment. The extensive intermolecular hydrogen bonding in the crystal has been identified by the shifting of bands due to the stretching and bending modes of the various functional groups. The sulfate group forms the anion. Its fundamentals continue to be degenerate except for the asymmetric bending mode and it suggests that the T(d) symmetry of SO(4)(2-) group has not been affected in the crystal.

Aspartic Acid↗
PubMed1980

Acute central stimulation of luteinizing hormone by parenterally administered N-methyl-D,L-aspartic acid in the male rat.

N-methyl-D,L-aspartic acid (NMA), a potent neuroexcitatory and neurotoxic glutamic acid analogue, acutely elevated serum luteinizing hormone (LH) in male rats when given subcutaneously in doses below those that cause morphologically detectable hypothalamic neurotoxicity. NMA treatment in doses known to be subtoxic by morphological criteria fails to induce any permanent neuroendocrine dysfunction as assessed by several physiological parameters, including NMA responsiveness after multiple consecutive dosees spaced at 24 h intervals, subsequent basal LH levels and subsequent postcastration LH elevations. Like naloxone, NMA elevates serum LH by reversibly stimulating a central labile pool. Neither has a direct stimulatory effect on the pituitary in vitro. Treatment with either attenuates naloxone-induced LH stimulation 2 h, but not 14 days, later while pituitary responsiveness to LHRH in vivo remains unaltered. Neither NMA nor naloxone is dependent upon testosterone for its LH stimulatory action and both increase serum LH through physiological mechanisms responsive to testosterone inhibition. It is concluded that subtoxic LH stimulating doses of NMA provide a useful tool in discerning neurotransmitter systems involved in central control of the hypothalamic-pituitary-gonadal axis.

Animals↗
PubMed1980

Embryotoxicity in mice of phosphonacetyl-L-aspartic acid (PALA), a new antitumor agent. II. Studies on its mechanism and reversibility.

The embryolethal effects of phosphonacetyl-L-aspartic acid (PALA) are markedly gestational stage-specific in the Swiss albino mouse. Embryos are most sensitive to the lethal effects of PALA on days 7 and 8 of gestation, with embryonic LD50's of 9 and 8 mg/kg, respectively. In contrast, the embryonic LD50 on day 10 of gestation is 144 mg/kg. Following an IP dose of (acetyl-14C)-PALA to pregnant mice, approximately threefold higher levels of radioactivity were present in day 8 than in day 10 embryonic tissue, whereas the radioactive content of placentas from day 10 pregnant animals was significantly higher than in placentas from day 8 pregnant mice. Similarly, L-aspartate transcarbamylase (ATCase) activity was greater in maternal spleen, placentas, and embryos on day 8 than on day 10 of gestation, and PALA treatment produced a greater inhibition of ATCase in embryonic tissue on day 8 than on day 10; however, inhibition of placental ATCase activity was more pronounced on day 10 than on day 8. Neither single nor multiple doses of uridine (UR) given orally to pregnant mice on day 8 of gestation were effective in reducing day 8 PALA embryolethality. Carbamyl-L-aspartic acid, given in the drinking water of pregnant mice on days 7-9 of gestation, reduced the day 8 embryolethality of PALA from 100% to approximately 50%. In a similar experiment, the presence of UR in the drinking water of pregnant mice reduced PALA-induced embryolethality in day 10, but not day 8, embryos. These results indicate that the embryotoxic effects of PALA are the result of ATCase inhibition; furthermore, they suggest that the relative insensitivity of the day 10 embryo to the lethal effects of PALA may result either from a greater availability of UR to the day 10 (versus the day 8) embryo, or from an enhanced ability of the day 10 placenta to bind PALA and prevent its passage into the embryo.

Animals↗
PubMed1976

4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole as a reactivity probe for the investigation of the thiol proteinases. evidence that ficin and bromelain may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain.

1. 4-Chloro-7-nitrobenzo-2-oxa-1,3-diazole (Nbd chloride) was used as a reactivity probe to characterize the active centres of papin (EC 3.4.22.2), ficin (EC 3.4.22.3) and bromelain (EC 3.4.22.4). 2. In the pH range 0-8 Nbd chloride probably exists mainly as a monocation, possibly with the proton located on N-1 of the oxadiazole ring. 3. Spectroscopic evidence is presented for the intermediacy of Meisenheimer-type adducts in the reaction of Nbd chloride with nucleophiles. 4. The pH-dependence of the second-order rate constants (k) of the reactions of the three enzymes with Nbd chloride was determined at 25 degrees C, I = 0.1 mol/litre in 6.7% (v/v) ethanol in the pH range 2.5-5, where, at least for papain and ficin, the reactions occur specifically with their active-centre thiol groups. The pH-k profile for the papain reaction is bell-shaped (pKaI = 3.24, pKaII = 3.44 and k = 86M(-1)-s(-1), whereas that for ficin is sigmoidal (pKa = 3.6, k = 0.36M(-1)-s(-1), the rate increasing with increasing pH. The profile for the bromelain reaction appears to resemble that for the ficin reaction, but is complicated by amino-group labelling. 5. The bell-shaped profile of the papain reaction is considered to arise from the reaction of the thiolate ion of cysteine-25, maintained in acidic media by interaction with the side chain of histidine-159, with the Nbd chloride monocation hydrogen-bonded at its nitro group to the un-ionized form of the carboxyl group of aspartic acid-158. The lack of acid catalysis in the corresponding reactions of ficin and probably of bromelain suggests that these enzymes may lack carboxyl groups conformationally equivalent to that of aspartic acid-158 of papain. The possible consequences of this for the catalytic sites of these enzymes is discussed.

4-Chloro-7-nitrobenzofurazan↗
PubMed1991

Aspartic acid at position 57 of the HLA-DQ beta chain is protective against future development of insulin-dependent (type 1) diabetes mellitus.

Insulin-dependent (Type I) diabetes mellitus is a chronic autoimmune disease. From studies in discordant twins and multiplex families a long prediabetic period has been reported. In a population-based program started in 1983, fifteen individuals at possible risk for future Type I diabetes were followed for up to 74 months. Two individuals (13%) developed Type I diabetes. These probands were characterized by the presence of high-level cytoplasmic islet cell antibodies (ICA), complement-fixing ICA, and an impaired first-phase insulin response after intravenous glucose load. Both were homozygous for a high-risk immunogenetic marker of Type I diabetes, i.e., non-Asp at codon 57 of the HLA-DQ beta chain. In all other subjects studied, the immunogenetic marker that confers "dominant resistance", aspartic acid at codon 57, was found. On the basis of our data we conclude that a combination of assays which determine ICA, first-phase insulin release, and HLA-DQB1 polymorphisms will identify individuals with a high probability of developing Type I diabetes at the population level. Conversely, HLA haplotypes positive for aspartic acid seem to confer resistance to the disease.

Adult↗
PubMed2001

HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against development of rheumatoid arthritis.

OBJECTIVE: To determine whether the association between rheumatoid arthritis (RA) and HLA-DRB1 is influenced by the amino acid residue encoded at position 70 (beta70) of the third hypervariable region (HVR3) of the HLA-DRbeta chain. METHODS: The frequencies of HLA-DRB1 alleles encoding different amino acid residues at beta70 were compared between patients with RA and controls in a population from the UK and in a confirmatory population from northwestern Spain. HLA-DRB1 typing was done by polymerase chain reaction methods on 476 clinic based patients with RA and 180 healthy controls from Staffordshire and Cheshire in the UK, and on 179 clinic patients and 145 controls from Lugo, Spain. Associations were investigated using chi-square analyses and regression analyses. The extended Mantel-Haenszel procedure was used for trend analysis. RESULTS: Carriage of 2 shared epitope (SE)+ alleles encoding a glutamine at beta70 (Q70SE+/Q70SE+) was associated with the greatest risk of RA in the UK and Spanish population (odds ratios 7.93 and 4.66, respectively), while possession of 2 SE- alleles encoding an aspartic acid at beta70 (D70SE-D70SE-) was associated with the lowest risk (OR 0.23 and 0.34, respectively). In individuals carrying one SE+ allele and an accompanying D70SE- allele there was no increased risk of developing RA [OR 0.93 (UK) and 1.30 (Spain)]. Possession of D70SE- was more strongly protective than possession of Q70SE. Analysis of trend indicated that the strength of association of different DRB1 genotypes with RA could be ranked in order (from Q70SE+/Q70SE+ to D70SE-/D70SE-) according to which amino acid residues were encoded at beta70, and whether or not they formed part of a SE sequence. The severity of radiographic damage could not be ranked in the same fashion. CONCLUSION: The amino acid residue at position 70 of the HVR3 in HLA-DRbeta molecules influences susceptibility to RA. The strength of the association of DRB1 genotypes with RA is dependent not only on SE status, but also on which amino acid residues are encoded at beta70 of the DRB1 alleles. Presence of an aspartic acid residue at beta70 protects against development of RA. However, the severity of erosive damage does not appear to be associated with the amino acid substitution at 1370.

Alleles↗
PubMed1995

Estimation of age from dentin by using the racemization reaction of aspartic acid.

To confirm the usefulness of the whole dentin in longitudinal sections for estimating age using the racemization ratio (D/L ratio) of aspartic acid, we compared longitudinal and transverse sections prepared from bilateral teeth in the same jaw of the same subjects. The D/L ratio was measured by gas chromatography. A better correlation between the D/L ratio and true age was observed when using longitudinal sections (r = 0.995) than when using transverse sections (r = 0.984-0.987). In the low age group, the D/L ratio was high in the crown and decreased toward the root apex. In the middle-advanced age groups, however, the D/L ratio was high in the crown as well as the area close to the root apex. The racemization reaction rate was higher in longitudinal than in transverse sections. These results suggest that the whole dentin in longitudinal sections of the central area of the tooth should be examined for accurate estimation of age.

Adolescent↗
PubMed1996

Regulation of growth hormone secretion by amino acid neurotransmitters in the goldfish (I): Inhibition by N-methyl-D, L-aspartic acid.

High levels of the amino acid neurotransmitter glutamate were found in the goldfish hypothalamus and pituitary using high performance liquid chromatography with fluorometric detection. A specific polyclonal antibody to glutamate was generated in the rabbit for immunocytochemistry. Localization studies demonstrated that glutamatergic neurons of undetermined origin innervate the particular part of the goldfish adenohypophysis where somatotrophs and gonadotrophs are located. Intraperitoneal and brain third ventricle injection of the glutamate agonist N-methyl-D,L-aspartic acid (NMA) inhibited GH release in vivo. The gonadal steroid estradiol plays an important role in regulating GH secretion by stimulating basal serum GH levels and enhancing the inhibitory effects of NMA on GH secretion. Taken together, these results demonstrate that glutamate is an important regulator of GH secretion in goldfish.

Animals↗
PubMed1993

Occurrence of free D-aspartic acid in the circumsoesophageal ganglia of Aplysia fasciata.

This study reports the presence of high concentrations of free D-aspartic acid (D-Asp) in the circumoesophageal ganglia of the opisthobranch mollusc Aplysia fasciata. D-Asp was discovered using specific methods that employ Octopus D-aspartate oxidase and hog kidney D-amino acid oxidase to measure D-Asp levels. The concentration of D-Asp was 0.281 mumol/g wet tissue weight, which was 8.3% of the total free aspartic acid (D and L forms) present. No other free D-amino acids that were oxidised by D-amino acid oxidase were detected. To our knowledge the only molluscs that have previously been shown to have D-Asp within their nervous tissue are the cephalopods Octopus vulgaris, Loligo vulgaris and Sepia officinalis. In these, as in A. fasciata, no other D-amino acids were detected within the nervous tissue. The fact that free D-Asp occurs specifically in the nervous tissue of the above molluscs suggests that it may have a neurological function that is yet to be described.

Animals↗
PubMed1991

Cholinesterase-like domains in enzymes and structural proteins: functional and evolutionary relationships and identification of a catalytically essential aspartic acid.

Primary sequences of cholinesterases and related proteins have been systematically compared. The cholinesterase-like domain of these proteins, about 500 amino acids, may fulfill a catalytic and a structural function. We identified an aspartic acid residue that is conserved among esterases and lipases (Asp-397 in Torpedo acetylcholinesterase) but that had not been considered to be involved in the catalytic mechanism. Site-directed mutagenesis demonstrated that this residue is necessary for activity. Analysis of evolutionary relationships shows that the noncatalytic members of the family do not constitute a separate subgroup, suggesting that loss of catalytic activity occurred independently on several occasions, probably from bifunctional molecules. Cholinesterases may thus be involved in cell-cell interactions in addition to the hydrolysis of acetylcholine. This would explain their specific expression in well-defined territories during embryogenesis before the formation of cholinergic synapses and their presence in noncholinergic tissues.

Acetylcholinesterase↗
PubMed2001

Comparison and evaluation of the synthetic biopolymer poly-L-aspartic acid and the synthetic "plastic" polymer poly-acrylic acid for use in metal ion-exchange systems.

Poly-L-aspartic acid (PLAsp), a biopolymer, and a similar synthetic polymer, poly-acrylic acid (PAA), each consisting of approximately 50 repeating Asp and acrylic acid monomers, respectively, were immobilized onto controlled pore glass (CPG) and evaluated for use as metal ion-exchange materials. Both polymers achieve metal complexation primarily through their repeating carboxylate side groups resulting in a similar binding trend for the metals tested (Ca(2+), Cd(2+), Co(2+), Cu(2+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+)), with metal binding capacities ranging from <0.1 to 12 micromol metal/g column and <0.1 to 32 micromol metal/g column for PLAsp and PAA respectively. Cu(2+) and Pb(2+) exhibited strong binding to both materials, while the other metals demonstrated only weak or minimal binding. Both columns allowed for quantitative release of bound metals through acid stripping and experienced increased overall metal binding with increasing pH. Both systems also maintained similar structural and chemical stability when continuously exposed to neutral buffered, highly acidic, oxidizing, large molecule rich, and elevated temperature environments. The main differences between the two systems are the material cost and system biodegradability.

Acrylates↗
PubMed2004

His-404 and His-405 are essential for enzyme catalytic activities of a bacterial indole-3-acetyl-L-aspartic acid hydrolase.

Bacterial indole-3-acetyl-l-aspartic acid (IAA-Asp) hydrolase has shown very high substrate specificity compared with similar IAA-amino acid hydrolase enzymes found in Arabidopsis thaliana. The IAA-Asp hydrolase also exhibits, relative to the Arabidopsis thaliana-derived enzymes, a very high Vmax (fast reaction rate) and a higher Km (lower substrate affinity). These two characteristics indicate that there are fundamental differences in the catalytic activity between this bacterial enzyme and the Arabidopsis enzymes. By employing a computer simulation approach, a catalytic residue, His-385, from a non-sequence-related zinc-dependent exopeptidase of Pseudomonas was found to structurally match His-405 of IAA-Asp hydrolase. The His-405 residue is conserved in all related sequences of bacteria and Arabidopsis. Point mutation experiments of this His-405 to seven different amino acids resulted in complete elimination of enzyme activity. However, point mutation on the neighboring His-404 to eight other residues resulted in reduction, to various degrees, of enzyme activity. Amino acid substitutions for His-404 also showed that this residue influenced the minor activity of the IAA-Asp hydrolase for the substrates IAA-Gly, IAA-Ala, IAA-Ser, IAA-Glu and IAA-Asn. These results show the value and potential of structural modeling for predicting target residues for further study and for directing bioengineering of enzyme structure and function.

Amino Acid Sequence↗