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At least 793 records · Page 44Linked to original sources
PubMed1998

Mutagenesis of the aspartic acid ligands in human serum transferrin: lobe-lobe interaction and conformation as revealed by antibody, receptor-binding and iron-release studies.

Recombinant non-glycosylated human serum transferrin and mutants in which the liganding aspartic acid (D) in one or both lobes was changed to a serine residue (S) were produced in a mammalian cell system and purified from the tissue culture media. Significant downfield shifts of 20, 30, and 45 nm in the absorption maxima were found for the D63S-hTF, D392S-hTF and the double mutant, D63S/D392S-hTF when compared to wild-type hTF. A monoclonal antibody to a sequential epitope in the C-lobe of hTF reported affinity differences between the apo- and iron-forms of each mutant and the control. Cell-binding studies performed under the same buffer conditions used for the antibody work clearly showed that the mutated lobe(s) had an open cleft. It is not clear whether the receptor itself may play a role in promoting the open conformation or whether the iron remains in the cleft.

Antigen-Antibody Reactions↗
PubMed1988

Ultrastructural characterization of gerbil olivocochlear neurons based on differential uptake of 3H-D-aspartic acid and a wheatgerm agglutinin-horseradish peroxidase conjugate from the cochlea.

Two populations of olivocochlear (OC) neurons have been identified in the gerbil brain stem on the basis of differential labeling patterns of 3H-D-aspartic acid (D-ASP) and wheatgerm agglutinin-horseradish peroxidase conjugate (WGA/HRP) from the cochlear perilymph. While both populations are capable of uptake and retrograde uptake of WGA/HRP, one population accumulates and retrogradely transports D-ASP (D-ASP OC neurons) and the other does not (non-D-ASP OC neurons). D-ASP OC neurons are found in or near the lateral superior olive, are small in size, and receive very few synaptic contacts. The vast majority of these synapses contain small, mildly pleomorphic vesicles with scattered dense core vesicles. Synapses with distinctly larger pleomorphic vesicles have also been observed. These neurons possess all of the features common to neurons of the lateral olivocochlear system. Non-D-ASP OC neurons are found primarily in the ventral nucleus of the trapezoid body, as well as in the area between the medial superior olive and the medial nucleus of the trapezoid body. These neurons are larger and receive greater numbers and types of synaptic contacts than those found on D-ASP OC neurons. The 2 most common synapses found on non-D-ASP OC neurons are axosomatic ones containing small, mildly pleomorphic vesicles and scattered dense core vesicles similar to those seen on the D-ASP OC neurons, and axodendritic synapses containing large, round vesicles. Much less frequently observed are synapses containing small, round vesicles or ones containing predominantly flat vesicles. The ultrastructural features of the non-D-ASP OC neurons correspond to those described for neurons of the medial olivocochlear system.

Animals↗
PubMed2006

Aspartic acid homozygosity at codon 57 of HLA-DQ beta is associated with susceptibility to pulmonary tuberculosis in Cambodia.

After infection with Mycobacterium tuberculosis, clinical disease usually remains latent, contained by the host immune response. Although polymorphisms of HLA loci have been hypothesized to play a major role in the breakdown of latency, a functional link has not been established. Molecular-based HLA-typing methods were used to test the association of sets of HLA alleles encoding an aspartic acid at codon 57 of the HLA-DQ beta-chain (HLA-DQ beta57-Asp) with susceptibility to tuberculosis in a cohort of 436 pulmonary tuberculosis patients and 107 healthy controls from Cambodia. HLA class II null cells were transduced with HLA-DQ beta57-Asp or HLA-DQ beta57-Ala and evaluated for their ability to bind peptides from two immunogenic M. tuberculosis specific proteins, ESAT-6 and CFP-10. In this study, we report a highly significant association between progressive pulmonary tuberculosis and homozygosity for HLA-DQ beta57-Asp alleles. The presence of HLA-DQ beta57-Asp resulted in a significantly reduced ability to bind a peptide from the central region of the ESAT-6 protein. Furthermore, when this peptide was presented by an HLA-DQ beta57-Asp allele, Ag-specific IFN-gamma production from CD4+ T cells from tuberculosis patients was significantly less than when this peptide was presented by an HLA-DQ-beta allele encoding an alanine at codon 57. Multiple genetic loci and ethnic-specific factors are likely involved in the human immune response to tuberculosis. The data presented here provide a functional explanation for a highly significant association between an HLA polymorphism and tuberculosis in a highly characterized group of patients with susceptibility to progressive tuberculosis infection in Cambodia.

Adolescent↗
PubMed1990

Modulation of N-methyl-D-aspartic acid receptor desensitization by glycine in mouse cultured hippocampal neurones.

1. Responses to N-methyl-D-aspartic acid (NMDA) were recorded from mouse embryonic hippocampal neurones in dissociated culture, using the tight-seal, whole-cell, patch-clamp technique for voltage clamp. A rapid perfusion system, with an exchange time constant of less than 10 ms, was used to apply NMDA under conditions which minimized slow, calcium-sensitive desensitization. With no added glycine, responses to 100 microM-NMDA applied for 1.5 s declined by greater than 90%, due to an additional component of desensitization of time constant 250 ms. 2. Adding glycine to the extracellular solution, over the range 30 nM to 3 microM, both potentiated responses to NMDA and to L-glutamate, and reduced fast desensitization. In the presence of 3 microM-glycine responses to NMDA declined by only 10%. Similar potentiation and reduction of desensitization was obtained with 3 microM concentrations of the glycine analogues D-alanine and D-serine. 3. Analysis of dose-response curves for the action of glycine on responses to 100 microM-NMDA revealed a 3-fold higher potency of glycine for potentiation of peak versus steady-state responses, with concentrations for half-activation of 134 and 382 nM, respectively. The competitive glycine antagonist 7-chlorokynurenic acid produced a similar shift of both the peak and steady-state dose-response curves for glycine, consistent with an equilibrium dissociation constant of 280 nM for interaction of 7-chlorokynurenic acid with the glycine binding site on NMDA receptors. 4. In the presence of 100 nM-glycine, 10 microM-7-chlorokynurenic acid produced nearly complete block of the response to 3 nM-NMDA, suggesting that glycine is absolutely required for activation of the NMDA receptor channel complex. 5. In some neurones responses to NMDA showed essentially no desensitization in the presence of 3 microM-glycine. Under these conditions, 7-chlorokynurenic acid produced a concentration-dependent block of both the initial and equilibrium response to NMDA, with a 4-fold greater sensitivity for block of the steady-state current (IC50 = 2.25 microM) than for block of the peak current (IC50 = 8.96 microM). As a result, in the presence of 7-chlorokynurenic acid, responses to NMDA showed strong desensitization, even in the presence of 3 microM-glycine. 6. Our results show that glycine-evoked potentiation of NMDA receptor activity is accompanied by reduced desensitization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[Determination of taurine, L-glutamine, vitamin U and L-aspartic acid in pharmaceuticals by high-performance liquid chromatography with pre-column derivatization].

A pre-column derivatization method for the high-performance liquid chromatographic determination of taurine (1), L-glutamine (2), vitamin U (3) and L-aspartic acid (4) in pharmaceuticals has been developed. The optimum requirements for the derivatization conditions and the stability of resulting derivatives were discussed. The compounds were converted into DNT derivatives through the amino group by reaction with sodium 2,6-dinitro-4-trifluoromethylbenzenesulfonate (DNTS) in 50% sodium borate at 60 degrees C for 30 min (1), at 60 degrees C for 90 min (2), at 60 degrees C for 80 min (3) and at 80 degrees C for 90 min (4). After the reaction mixtures were acidified with dil. HCl, the derivatives were separated on a Cosmosil 3C18 (4.6 mm i.d. x 50 mm) column using 1% acetic acid-methanol (13:7) containing 2 mM sodium 1-heptanesulfonate as mobile phase with a ultra violet detector at 280 nm. The precisions of the analytical values expressed as the coefficient of variation were below 2.0%. The recoveries of 1-4 added to various commercial samples were in the range of 97.8-100.6%.

Aspartic Acid↗
PubMed1993

Use of poly-l-aspartic acid to inhibit aminoglycoside cochlear ototoxicity.

Gentamicin is an extremely effective antibiotic against a wide variety of organisms. However, its use is limited by its nephrotoxic and ototoxic effects. Recent studies in rats have shown that poly-l-aspartic acid (PAA) effectively blocks the nephrotoxic effects of the aminoglycosides and does not decrease the antibiotic effectiveness of gentamicin against those organisms tested. A controlled test was undertaken to evaluate the effect of PAA on cochlear ototoxicity. Test solutions were administered to four groups of guinea pigs for 10 days. Group 1, the controls, received distilled water, group 2 received gentamicin, group 3 received PAA, and group 4 received gentamicin plus PAA. Auditory brainstem response thresholds at 20, 16, 8, and 4 kHz were obtained before therapy, after completion of the 10-day course, and 21 days following the completion of therapy. Two-dimensional diffusion assays in human serum were performed to evaluate the effect of PAA on the antimicrobial activity. Histologic evaluation of the cochleae was performed at the conclusion of the experiment. Threshold shifts following 10 days of therapy were not statistically significant in group 4 compared to controls, while the gentamicin group (group 2) was significantly different for all frequencies tested. At 21 days following therapy, group 4 (PAA + gentamicin) maintained significance in the higher frequencies studied. Antimicrobial studies demonstrated that PAA has no effect on the antimicrobial activity of gentamicin and has no antimicrobial effect against Bacillus subtilis when used alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Complete identification of C = O stretching vibrational bands of protonated aspartic acid residues in the difference infrared spectra of M and N intermediates versus bacteriorhodopsin.

Fourier transform infrared difference spectra were obtained for the M and N intermediates versus light-adapted bacteriorhodopsin (BR) with site-directed mutant proteins in which aspartic acid residues at positions 96 and 115 were replaced by asparagine. The positive and negative bands at 1740 and 1732 cm-1 in the M/BR spectrum are shown to be the superposition of bands due to C = O stretching vibrations of Asp-96 and Asp-115 (a positive band at 1736 cm-1 and a negative band at 1742 cm-1 of Asp-96, and a positive band at 1742 cm-1 and a negative band at 1734 cm-1 of Asp-115). The positive band at 1738 cm-1 and the negative band at 1734 cm-1 in the N/BR spectrum are attributed to Asp-115. On the basis of these results, Asp-115 is protonated in M and N as well as in the ground state. On the other hand, no bands corresponding to Asp-212 were found in the region of protonated carboxylic acid vibration, indicating that Asp-212 remains unprotonated in M and N. The frequencies of the C = O stretching modes of protonated Asp-96 and Asp-115 change in the opposite direction in the BR-to-M conversion relative to the shifts in the BR-to-L conversion, indicating different environmental changes for these residues in L and M.

Asparagine↗
PubMed2006

Neutralization of the aspartic acid residue Asp-367, but not Asp-454, inhibits binding of Na+ to the glutamate-free form and cycling of the glutamate transporter EAAC1.

Substrate transport by the plasma membrane glutamate transporter EAAC1 is coupled to cotransport of three sodium ions. One of these Na(+) ions binds to the transporter already in the absence of glutamate. Here, we have investigated the possible involvement of two conserved aspartic acid residues in transmembrane segments 7 and 8 of EAAC1, Asp-367 and Asp-454, in Na(+) cotransport. To test the effect of charge neutralization mutations in these positions on Na(+) binding to the glutamate-free transporter, we recorded the Na(+)-induced anion leak current to determine the K(m) of EAAC1 for Na(+). For EAAC1(WT), this K(m) was determined as 120 mm. When the negative charge of Asp-367 was neutralized by mutagenesis to asparagine, Na(+) activated the anion leak current with a K(m) of about 2 m, indicating dramatically impaired Na(+) binding to the mutant transporter. In contrast, the Na(+) affinity of EAAC1(D454N) was virtually unchanged compared with the wild type transporter (K(m) = 90 mm). The reduced occupancy of the Na(+) binding site of EAAC1(D367N) resulted in a dramatic reduction in glutamate affinity (K(m) = 3.6 mm, 140 mm [Na(+)]), which could be partially overcome by increasing extracellular [Na(+)]. In addition to impairing Na(+) binding, the D367N mutation slowed glutamate transport, as shown by pre-steady-state kinetic analysis of transport currents, by strongly decreasing the rate of a reaction step associated with glutamate translocation. Our data are consistent with a model in which Asp-367, but not Asp-454, is involved in coordinating the bound Na(+) in the glutamate-free transporter form.

Amino Acid Sequence↗
PubMed1999

A review of the methodological aspects of aspartic acid racemization analysis for use in forensic science.

Accurate age determination of adult cadavers and human remains is a key requirement in forensic practice. The current morphological methods lack accuracy and precision, require specialist training and are costly. The use of aspartic acid racemization (AAR) in human dentine provides a simple, cost-effective solution and the method can achieve accuracies of +/- 3 years at best. Currently, there are differences in AAR methodology between laboratories which produce different results on the rate of racemization in teeth. These inconsistencies must be resolved if the technique is to be successfully applied to age determinations in forensic cases. This paper reviews the differences in protocol which have been used, discusses how each method will affect the results obtained from AAR analysis and gives recommendations for optimization of the methological protocol as a first step towards international standardization.

Adult↗
PubMed1990

The extent of aspartic acid racemization in dentin: a possible method for a more accurate determination of age at death?

In the current study the objective was to find to what extent a reliable determination of age at death is made possible by establishing the degree of aspartic acid racemization in the dentin of teeth. The results of the investigation of 46 teeth are in agreement with the values found by other authors. The method presented makes a reproducible and accurate estimation of age possible. We intend to elaborate and improve this promising method for determination of age at death. The relevant points are presented here.

Adolescent↗
PubMed1989

Partial diversion of a mutant proinsulin (B10 aspartic acid) from the regulated to the constitutive secretory pathway in transfected AtT-20 cells.

A patient with type II diabetes associated with hyperproinsulinemia has been shown to have a point mutation in one insulin gene allele, resulting in replacement of histidine with aspartic acid at position 10 of the B-chain. To investigate the basis of the proinsulin processing defect, we introduced an identical mutation in the rat insulin II gene and expressed both the normal and the mutant genes in the AtT-20 pituitary corticotroph cell line. Cells expressing the mutant gene showed increased secretion of proinsulin relative to insulin and rapid release of newly synthesized proinsulin. Moreover, the mutant cell lines did not store the prohormone nor did they release it upon stimulation with secretagogues. These data indicate that a significant fraction of the mutant prohormone is released via the constitutive secretory pathway rather than the regulated pathway, thereby bypassing granule-related processing and regulated release.

Animals↗
PubMed1979

Immobilization of Escherichia coli cells containing aspartase activity with kappa-carrageenan. Enzymic properties and application for L-aspartic acid production.

Whole cells of Escherichia coli having high aspartase (L-asparate ammonialyase, EC 4.3.1.1) activity were immobilized by entrapping into a kappa-carrageenan gel. The obtained immobilized cells were treated with glutaraldehyde or with glutaraldehyde and hexamethylenediamine. The enzymic properties of three immobilized cell preparations were investigated, and compared with those of the soluble aspartate. The optimum pH of the aspartase reaction was 9.0 for the three immobilized cell preparations and 9.5 for the soluble enzyme. The optimum temperature for three immobilized cell preparations was 5--10 degrees C higher than that for the soluble enzyme. The apparent Km values of immobilized cell preparations were about five times higher than that of the soluble enzyme. The heat stability of intact cells was increased by immobilization. The operational stability of the immobilized cell columns was higher at pH 8.5 than at optimum pH of the aspartase reaction. From the column effluents, L-aspartic acid was obtained in a good yield.

Ammonia-Lyases↗
PubMed1990

A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones.

1. Responses to N-methyl-D-aspartic acid (NMDA) were recorded from mouse embryonic hippocampal neurones in dissociated culture, using whole-cell patch-clamp recording. A fast perfusion system, with an exchange time constant of less than 10 ms, was used to study modulation of NMDA receptor desensitization by glycine. 2. The onset of NMDA receptor desensitization was well fitted by a single-exponential function; with 30 nM-glycine the time constant was 250 ms, corresponding to a rate of 4 s-1. The rate of onset of desensitization became faster with increasing glycine concentration, with a slope of 0.87 x 10(7) M-1 s-1. Recovery from desensitization, studied with a twin-pulse technique, was also well fitted by a single-exponential function; with 30 nM-glycine the time constant of recovery was 1.95 s-1. The rate of recovery from desensitization became faster with increasing glycine concentration, with a slope of 0.76 x 10(7) M-1 s-1. These results are consistent with a model in which the effect of glycine occurs via an increase in the rate constant for recovery from desensitization, with little effect on the rate constant for onset of desensitization. Over the range 30-300 nM-glycine, the ratio of the rate constants calculated for recovery and onset of desensitization was a good predictor of the degree of desensitization recorded at equilibrium. 3. Concentration jump experiments with glycine were performed with 100 microM-NMDA present continuously, and for a single binding site model gave estimates of the association (1.1 x 10(7) M-1 s-1) and dissociation (3.1 s-1) rate constants for interaction of glycine with the NMDA receptor. In the presence of NMDA, concentration jumps from 3 microM-glycine to lower concentrations gave relaxations which became slower with decreasing glycine concentration over the range 1 microM-30 nM. A similar slowing of desensitization occurred when the glycine concentration was altered over the same range. 4. Glycine analogues of lower affinity produced desensitization with faster kinetics. D-Alanine, 150 nM, produced desensitization with a time constant of 175 ms, faster than recorded with an equipotent concentration of glycine (50 nM, time constant 259 ms). Responses of similar peak amplitude, recorded with 60 microM-L-alanine, and 500 microM-D,L-homoserine, did not produce strong desensitization, consistent with desensitization too rapid to resolve in our experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗
PubMed1982

The effects of D- and/or L-aspartic acids on the total weight of body, the weights of certain organs, and their protein, triglyceride and glycogen content.

125 rats which were divided into five groups were deprived of food or given orally D- (a potent inhibitor for L-asparaginase) and/or L-aspartic acids (Asp) for one week. The body weights before and at the end of the experiment were determined as well as post mortem the weights of brain, liver and kidneys, their protein contents, and the liver triglyceride and glycogen contents. D- and D+L-Asp caused significant decreases in the weights of body and liver, and in daily fluid intake; in addition liver and kidney protein, and liver triglyceride and glycogen contents were found to be lower than control. On the other hand, the food-deprived group which was subjected to more or less the same body weight loss due to food deprivation showed only a decrease in the liver triglyceride content. Since D-amino acids cause naloxone reversible analgesia which is, thus, considered as an involvement of endorphinergic system and of vasopressin, the effects of D-Asp were attributed to the changes in the availability of opioids and vasopressin, which simultaneously have an effect on each other as well as an effect of the release of ACTH. L-Asp appeared to antagonize the effects of D-Asp. Because L-Asp antagonizes the acute and chronic effects of morphine, including that on L-asparaginase activity, the hypothesis is proposed that the antagonizing effects of L-Asp observed may be caused at the level of L-asparaginase activity.

Animals↗
PubMed2000

Quality assurance in age estimation based on aspartic acid racemisation.

Estimates of the age of living and dead individuals, obtained in order to answer legal or social questions, require minimum quality standards in order to guarantee data quality. We present an outline strategy (with recommendations) for the attainment of quality assurance in age estimation based on aspartic acid racemisation. The strategy is based on a definition of minimum standards for laboratories, including documentation of procedures, methodology and levels of expertise, and the formulation of guidelines for intralaboratory and interlaboratory quality control.

Age Determination by Teeth↗
PubMed1999

CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis.

The expression of osteopontin (OPN), CD44 variants, and integrins has been correlated with tumorigenesis and metastasis. Here we show that these proteins cooperate to enhance cell motility. First, we demonstrate that several different CD44 variants bind to OPN in an arginine-glycineaspartic acid-independent manner, but that the standard form of CD44 does not. These CD44 variants bind to both the amino- and COOH-terminal portions of OPN independently of the arginine-glycine-aspartic acid sequence, suggesting that multiple domains on OPN can be bound by the CD44 variants. Antibodies directed against the integrin beta1 subunit are able to inhibit this binding. The binding of CD44 variants to OPN is significantly augmented by both anti-CD44s and anti-CD44v antibodies. This augmentation by anti-CD44 antibodies is OPN specific and, again, can be blocked by anti-beta1 antibodies. Finally, we show that OPN binding by CD44 variants/beta1-containing integrins promotes cell spreading, motility, and chemotactic behavior.

Animals↗