Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ASPARTIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1975

beta-Decarboxylation of L-aspartic acid: a metal chelate-catalyzed reaction.

beta-decarboxylation of L-aspartic acid was observed in the system, pyridoxal: L-aspartic acid:aluminum(III), 1:100:1 when heated at 80 degrees for three hours. This reaction was followed by electronic spectroscopy and showed quantitative conversion of pyridoxal to pyridoxamine indicating decarboxylation of the ketimine. alpha-Methyl-L-aspartic acid was not decarboxylated indicating the presence of the alpha-proton and prior transamination as requirements for decarboxylation. When pyridoxamine and oxalo-2-propionic acid were reacted at pD 4.60, product analysis by nmr showed the presence of pyridoxamine and alpha-ketobutyric acid, indicating hydrolysis of the decarboxylated ketimine. Decarboxylation was fast compared to spontaneous decarboxylation. A mechanism is proposed for non-enzymatic decarboxylation and the previously suggested mechanism for the inactivation of the enzyme aspartate beta-decarboxylase is discussed.

Aluminum↗
PubMed1989

Substitution of membrane-embedded aspartic acids in bacteriorhodopsin causes specific changes in different steps of the photochemical cycle.

Millisecond photocycle kinetics were measured at room temperature for 13 site-specific bacteriorhodopsin mutants in which single aspartic acid residues were replaced by asparagine, glutamic acid, or alanine. Replacement of aspartic acid residues expected to be within the membrane-embedded region of the protein (Asp-85, -96, -115, or -212) produced large alterations in the photocycle. Substitution of Asp-85 or Asp-212 by Asn altered or blocked formation of the M410 photointermediate. Substitution of these two residues by Glu decreased the amount of M410 formed. Substitutions of Asp-96 slowed the decay rate of the M410 photointermediate, and substitutions of Asp-115 slowed the decay rate of the O640 photointermediate. Corresponding substitutions of aspartic acid residues expected to be in cytoplasmic loop regions of the protein (Asp-36, -38, -102, or -104) resulted in little or no alteration of the photocycle. Our results indicate that the defects in proton pumping which we have previously observed upon substitution of Asp-85, Asp-96, Asp-115, and Asp-212 [Mogi, T., Stern, L. J., Marti, T., Chao, B. H., & Khorana, H. G. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 4148-4152] are closely coupled to alterations in the photocycle. The photocycle alterations observed in these mutants are discussed in relation to the functional roles of specific aspartic acid residues at different stages of the bacteriorhodopsin photocycle and the proton pumping mechanism.

Alanine↗
PubMed1990

Increased aspartic acid release from the iron-induced epileptogenic focus.

Evidence has been growing in recent years for the involvement of excitatory neurotransmitter amino acids in the etiology of epilepsy. The precise mechanism of this involvement, however, remains unknown. In the present study, in vitro release and uptake of [3H]aspartic acid and [3H]glutamic acid were investigated in focal cerebral cortex in the iron-induced model of post-traumatic epilepsy in the rat. The animals were injected with FeCl3 or saline into the cerebral cortex and release and uptake studied in cortical slices from both acute and chronic foci (30 min and 3 weeks post injection, respectively), using a superfusion system. The results showed: (a) a significant increase in K(+)-stimulated aspartic acid release from the acute iron injected focus as compared to the corresponding saline injected cortex; and (b) no significant differences in the release of glutamic acid or in the uptake of glutamic acid and aspartic acid between the iron injected and the saline injected cortex. The finding of increased aspartic acid release suggests that this amino acid may play a role in the mechanism of iron-induced epilepsy in the rat.

Acute Disease↗
PubMed2004

Serum protein adsorption and platelet adhesion on aspartic-acid-immobilized polysulfone membranes.

Polysulfone (PSf) membranes that covalently conjugated with aspartic acid (ASP-PSf) were prepared and analyzed for hemocompatability. Compared to PSf or other types of surface-modified PSf membranes, the ASP-PSf membranes had a reduced ability to adsorb protein from either a plasma solution or a mixed solution of albumin, globulin and fibrinogen. This appears to be due to the creation of a hydrophilic surface by the aspartic acid zwitterion immobilized on the ASP-PSf membranes. Furthermore, the analyses of membrane protein adsorption showed that a mixed protein solution recapitulates the cooperative adsorption of proteins that occurs in plasma. We also found that the number of adhering platelets was the lowest on the ASP-PSf membranes and, in general, that platelet adhesion decreased in parallel with fibrinogen adsorption. In summary, aspartic acid immobilized on the ASP-PSf membranes, which have zwitterions with a net zero charge, effectively contributes to the hydrophilic and hemocompatible sites on the surface of the hydrophobic PSf membranes.

Adsorption↗
PubMed1995

Evidence that aspartic acid 301 is a critical substrate-contact residue in the active site of cytochrome P450 2D6.

Model building studies have intimated a role for aspartic acid 301 in the substrate binding of cytochrome P450 2D6 (CYP2D6). We have tested this hypothesis by generating a range of CYP2D6 mutants substituting a variety of amino acids at this site. The mutant proteins, which included substitution with a negatively charged glutamic acid residue or neutral asparagine, alanine, or glycine residues, were expressed in Saccharomyces cerevisiae. In addition, a mutant where aspartic acid 301 was deleted was also tested. All the mutants expressed approximately equivalent amounts of recombinant apoprotein and, apart from the alanine 301 and the aspartic acid 301 deletion mutants, gave carbon monoxide difference spectra of similar magnitude to the wild type. In the cases of the alanine and deletion mutants, the amount of holoprotein was significantly reduced or absent relative to the amount of apoprotein, indicating restricted heme incorporation. The glutamic acid mutant was shown to have similar catalytic properties to the wild type enzyme toward the substrates debrisoquine and metoprolol; however, some differences in regioselectivity and ligand binding were observed. The mutants containing neutral amino acids at position 301 exhibited marked reductions in catalytic activity. At low substrate concentrations little, if any, activity toward debrisoquine and metoprolol was measured. However, at a higher substrate concentration (2 mM) some activity was observed (about 10-20% of wild type levels). Consistent with the above findings, the debrisoquine-induced spin changes in the mutant proteins were markedly reduced. These data collectively demonstrate that aspartic acid 301 plays an important role in determining the substrate specificity and activity of CYP2D6 and provide experimental evidence supporting the role of this amino acid in forming an electrostatic interaction between the basic nitrogen atom in CYP2D6 substrates and the carboxylate group of aspartic acid 301.

Aspartic Acid↗
PubMed1988

A 13C-NMR study on the influxes into the tricarboxylic acid cycle of a renal epithelial cell line, LLC-PK1/Cl4: the metabolism of [2-13C]glycine, L-[3-13C]alanine and L-[3-13C]aspartic acid in renal epithelial cells.

Perchloric acid extracts of LLC-PK1/Cl4 cells, a renal epithelial cell line, incubated with either [2-13C]glycine L-[3-13C]alanine, or D,L-[3-13C]aspartic acid were investigated by 13C-NMR spectroscopy. All amino acids, except labelled glycine, gave rise to glycolytic products and tricarboxylic acid cycle (TCA) intermediates. For the first time we also observed activity of gamma-glutamyltransferase activity and glutathione synthetase activity in LLC-PK1 cells, as is evident from enrichment of reduced glutathione. Time courses showed that only 6% of the labelled glycine was utilized in 30 min, whereas 31% of L-alanine and 60% of L-aspartic acid was utilized during the same period. 13C-NMR was also shown to be a useful tool for the determination of amino acid uptake in LLC-PK1 cells. These uptake experiments indicated that glycine, alanine and aspartic acid are transported into Cl4 cells via a sodium-dependent process. From the relative enrichment of the glutamate carbons, we calculated the activity of pyruvate dehydrogenase to be about 61% when labelled L-alanine was the only carbon source for LLC-PK1/Cl4 cells. Experiments with labelled D,L-aspartic, however, showed that about 40% of C-3-enriched oxaloacetate (arising from a de-amination of aspartic acid) reached the pyruvate pool.

Alanine↗
PubMed1965

RELATIONSHIP OF CARBON DIOXIDE TO ASPARTIC ACID AND GLUTAMIC ACID IN ACTINOMYCES NAESLUNDII.

Buchanan, B. B. (Duke University, Durham, N.C.), and Leo Pine. Relationship of carbon dioxide to aspartic acid and glutamic acid in Actinomyces naeslundi. J. Bacteriol. 89:729-733. 1965.-CO(2), which was essential for the fermentation of glucose to succinic acid by Actinomyces naeslundii, was also required for the synthesis of internal aspartic acid, for which the cells lack a permease.

Actinomyces↗
PubMed1998

Changes in the amount of D-aspartic acid in the human femur with age.

The amount of D-aspartic acid (D/L ratio) among total amino acids, acid-insoluble collagen, and non-collagen proteins (acid-soluble peptides) from the human femoral compact substance was measured by gas chromatography. We found that the amount of D-aspartic acid increased linearly with age in males but not in females. This difference between the sexes may be related to the sex differences in hormonal circumstances to the fact that osteopathy is more common in females than in males. The D/L ratio in total amino acids varied with the size of the bone fractions, being higher in large ones. The D/L ratio in acid-soluble peptides varied with the size of the powder particles from which they had been extracted, and was also higher in large particles. It is concluded that D-aspartic acid in the femoral compact substance increases with age only in males.

Adolescent↗
PubMed1996

Design of protecting groups for the beta-carboxylic group of aspartic acid that minimize base-catalyzed aspartimide formation.

With the objectives of developing new protecting groups for the beta-carboxyl group of aspartic acid that are resistant to base-catalyzed aspartimide formation and of evaluating the importance of sterical factors in the design of such protecting groups, four new alkyl ester derivatives of aspartic acid were synthesized. The beta-3-pentyl, beta-4-heptyl, beta-2,6-dimethyl-4-heptyl and the recently described beta-2,4-dimethyl-3-pentyl esters of Boc-aspartic acid were incorporated into model peptides, and the resin-bound protected peptides were treated with 20% piperidine for 10 h. The levels of aspartimide-related side products were compared with the previously reported beta-cyclohexyl, beta-menthyl and beta-2-adamantyl esters of aspartic acid. The results show that bulky, acyclic, aliphatic protecting groups (in particular the 2,4-dimethyl-3-pentyl ester) are significantly more resistant to base-catalyzed aspartimide formation than comparably rigid cyclic alkyl esters that under the same reaction conditions form several-fold more aspartimide-related side products. Using elevated temperatures to overcome difficult couplings leads to the formation of significant amounts of aspartimide when aspartic acid is protected with the cyclohexyl group, but the 2,4-dimethyl-3-pentyl protecting group offers excellent protection under these conditions. The use of the 2,4-dimethyl-3-pentyl protecting group will allow the use of orthogonally removable base-labile protecting groups in Boc chemistry and suggests a design of protecting groups for other nucleophile-sensitive trifunctional amino acids in both Boc and Fmoc chemistry.

Aspartic Acid↗
PubMed2006

Conformation and structure of bis(glycyl-L-aspartic acid) oxalate 0.4-hydrate.

The title bis(glycyl-L-aspartic acid) oxalate complex {systematic name: bis[2-(2-ammonioacetamido)butanedioic acid] oxalate 0.4-hydrate}, 2C6H11N2O5+.C2O4(2-).4H2O, crystallizes in a triclinic space group with the planar peptide unit in a trans conformation. The asymmetric unit consists of two glycyl-L-aspartic acid molecules with positively charged amino groups and neutral carboxyl groups, and an oxalate dianion. The twist around the C-Calpha bond indicates that both the peptide molecules adopt extended conformations, while the twist around the N-Calpha bond shows that one has a folded and the other a semi-extended state. The present complex can be described as an inclusion compound with the dipeptide molecule as the host and the oxalate anion as the guest. The usual head-to-tail sequence of aggregation is not observed in this complex, as is also the case with the glycyl-L-aspartic acid dihydrate molecule. The study of aggregation and interaction patterns in binary systems is the first step towards understanding more complex phenomena. This further leads to results that are of general interest in bimolecular aggregation.

Crystallography, X-Ray↗
PubMed1991

Novel class of amino acid antagonists at non-N-methyl-D-aspartic acid excitatory amino acid receptors. Synthesis, in vitro and in vivo pharmacology, and neuroprotection.

The isoxazole amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid (AMPA) (1), which is a highly selective agonist at the AMPA subtype of excitatory amino acid (EAA) receptors, has been used as a lead for the development of two novel EAA receptor antagonists. One of the compounds, 2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionic acid (AMOA, 7), was synthesized via O-alkylation by ethyl chloroacetate of the amino acid protected AMPA derivative 4. The other compound, 2-amino-3-[2-(3-hydroxy-5-methylisoxazol-4-yl)-methyl-5-methyl-3-+ ++oxoisoxazolin -4-yl]propionic acid (AMNH, 14) was synthesized with use of 4-(chloromethyl)-3-methoxy-5-methylisoxazole (8) as the starting material. The intermediate 4-(chloromethyl)-2-(3-methoxy-5-methylisoxazol-4-yl)methyl-5-me thylisoxazolin- 3-one (11) was converted into the acetamidomalonate (12), which was stepwise deprotected to give 14. Compounds 7 and 14 were stable in aqueous solution at pH values close to physiological pH. Neither 7 nor 14 showed detectable affinities for the receptor, ion channel, or modulatory sites of the N-methyl-D-aspartic acid (NMDA) receptor complex. Quantitative receptor autoradiographic and conventional binding techniques were used to study the affinities of 7 and 14 for non-NMDA receptor sites. Both compounds were inhibitors of the binding of [3H]AMPA (IC50 = 90 and 29 microM, respectively). Compounds 14 and 7 were both very weak inhibitors of the high-affinity binding of radioactive kainic acid [( 3H]KAIN). Compound 14, but not 7, was, however, shown to be an inhibitor of low-affinity [3H]KAIN binding (IC50 = 40 microM) as determined in the presence of 100 mM calcium chloride. In the rat cortical slice preparation, 7 was shown to antagonize excitation induced by 1 with some selectivity, whereas 14 proved to be a rather selective antagonist of KAIN-induced excitation. Both antagonists showed very weak effects on the excitatory effects of NMDA. Compound 7 was a poor antagonist of excitation by quisqualic acid (2), whereas 14 did not affect excitation by this nonselective AMPA receptor agonist. On cat spinal neurones, both 7 and 14 reduced excitations by 1 and KAIN, but, again, the excitatory effects of 2 were much less sensitive. Compound 14 and, in particular, 7 effectively protected rat striatal neurones against the neurotoxic effects of KAIN, whereas the toxic effects of 1 were reduced only by 7. Neither antagonist showed protection against the cell damage caused by intrastriatal injection of the NMDA agonist quinolinic acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

The crystal structure of asparaginyl-tRNA synthetase from Thermus thermophilus and its complexes with ATP and asparaginyl-adenylate: the mechanism of discrimination between asparagine and aspartic acid.

The crystal structure of Thermus thermophilus asparaginyl-tRNA synthetase has been solved by multiple isomorphous replacement and refined at 2.6 A resolution. This is the last of the three class IIb aminoacyl-tRNA synthetase structures to be determined. As expected from primary sequence comparisons, there are remarkable similarities between the tertiary structures of asparaginyl-tRNA synthetase and aspartyl-tRNA synthetase, and most of the active site residues are identical except for three key differences. The structure at 2.65 A of asparaginyl-tRNA synthetase complexed with a non-hydrolysable analogue of asparaginyl-adenylate permits a detailed explanation of how these three differences allow each enzyme to discriminate between their respective and very similar amino acid substrates, asparagine and aspartic acid. In addition, a structure of the complex of asparaginyl-tRNA synthetase with ATP shows exactly the same configuration of three divalent cations as previously observed in the seryl-tRNA synthetase-ATP complex, showing that this a general feature of class II synthetases. The structural similarity of asparaginyl- and aspartyl-tRNA synthetases as well as that of both enzymes to the ammonia-dependent asparagine synthetase suggests that these three enzymes have evolved relatively recently from a common ancestor.

Adenosine Triphosphate↗
PubMed1982

Stimulation of growth of Mycobacterium lepraemurium in cell-free liquid medium by DL-aspartic acid.

The growth of M. lepraemurium in cell-free liquid medium was strongly stimulated by addition of DL-aspartic acid at a final concentration of 0.01% to 0.02% to ND and ND-5 media containing dextran and liposome. No effect of DL-aspartic acid was observed when it was added to ND and ND-5 media without dextran and liposome. Optimal pH of the culture medium is critical for the stimulating effect of DL-aspartic acid, and it varies with the composition of the medium; the optimal pH was 6.0 in ND medium containing dextran and liposome (NDLA), and was 6.6 in NDLA medium supplemented with alpha-ketoglutarate, 1-cysteine HCl, hemin, and cytochrome c (NDLA-5). A possible mechanism of the effect of aspartic acid is discussed.

Aspartic Acid↗
PubMed2003

Complexes of vanadium(III) with L-alanine and L-aspartic acid.

The equilibria of the complexation processes of V(3+) with L-alanine and L-aspartic acid in aqueous solution over a wide pH range (2-10) were studied by potentiometric and spectroscopic (UV-Vis, CD) methods. The results show that alanine forms complexes with V(3+) in the metal ion concentration range and at the ligand-to-metal ratios investigated, giving mononuclear species only. In ML(2) species, which dominate in the range pH 4-8, alanine acts as a bidendate ligand through O and N atoms. The complexation processes of V(3+) with aspartic acid are more complicated. In acidic solution (up to pH approximately 4) they are similar to those for alanine. In the higher pH region, however, there are complicated equilibria among mono- and various dinuclear species. These dinuclear species consist of carboxylic or mu-oxo bridges and differ from each other by the number of coordinated ligands and OH(-) groups. The solid phase of the V(III) complex with aspartic acid could be isolated from nonaqueous solution only. Spectroscopic (UV-Vis-IR) measurements and magnetic susceptibility data confirm the coordination of vanadium(III) by two carboxylic groups. Both V(III)-L-aspartic acid and V(III)-L-alanine complexes have a significant apoptotic effect on Hepatoma Morris 5123 cells.

Alanine↗
PubMed2003

Kinetic and mechanistic analysis of the association and dissociation of inhibitors interacting with secreted aspartic acid proteases 1 and 2 from Candida albicans.

In order to elucidate the characteristics of different aspartic proteases (Sap) secreted by Candida albicans, the kinetics of the interaction (k(on), k(off)) between Sap1 and Sap2 with acetyl-pepstatin and pepstatin A was determined at different pH by biosensor technology. The enzymes were biotinylated and coupled to a streptavidin-coated sensor chip, whereupon acetyl-pepstatin or pepstatin A was injected and the interaction was measured in real time. Sap2 showed a faster k(on) and a higher affinity for acetyl-pepstatin than Sap1, regardless of pH. The values for both k(on) and k(off) decreased with increased pH from 3.8 to 5.0, except for the k(off) for Sap1, which was only influenced by the pH change from 3.8 to 4.4. Binding of acetyl-pepstatin to Sap1 or Sap2 obviously proceeds by a different mechanism than dissociation of the inhibitor. Association appears to be coupled to protonation of a catalytic aspartic acid residue, consistent with reduced k(on) values at higher pH. In contrast, the stability of the complex is reduced at lower pH due to reduced hydrogen bonding capacity of aspartic acid residues acting as hydrogen bond acceptors. Differences in the number and distribution of charged nonactive site residues in Sap1 and Sap2 evidently result in different electrostatic properties of the binding sites, primarily influencing the association step.

Amino Acid Sequence↗
PubMed1993

Aspartic acid racemization in intervertebral discs as an aid to postmortem estimation of age at death.

We investigated whether measurement of aspartic acid racemization in intervertebral discs (IVD) could be used in the postmortem estimation of age at death. The extent of aspartic acid racemization in IVD tissues was found to increase with age. The rate of racemization turned out to be much higher in the nucleus pulposus than in the annulus fibrosus. The relation between age and the D-aspartic acid content in the anterior peripheral annulus fibrosus of IVD was close enough to allow postmortem estimation of age at death based on the extent of aspartic acid racemization in this tissue.

Adolescent↗
PubMed1987

Amino acid sequence of a soybean (Glycine max) seed polypeptide having a poly(L-aspartic acid) structure.

A polypeptide of Mr 4400 was isolated from soybean (Glycine max) seeds by extraction with 60% ethanol followed by ion-exchange and reverse-phase chromatography. The peptide contains an unusually high amount of aspartic acid residues (approximately 25%, and hence is designated as soybean aspartic acid-rich peptide). Its complete primary structure was determined by conventional methods to be the following. Ser-Lys-Trp-Gln-His-Gln-Gln-Asp-Ser-Cys-Arg-Lys-Gln-Leu-Gln-Gly-Val-Asn- Leu-Thr-Pro-Cys-Glu-Lys-His-Ile-Met-Glu-Lys-Ile-Gln-Gly-Arg-Gly-Asp-Asp- Asp-Asp-Asp-Asp-Asp-Asp-Asp A striking features of this primary structure is the presence of a poly(L-aspartic acid) sequence at the carboxyl terminus, and this polyaspartyl segment was found to precipitate bovine trypsin. The presence of the putative cell attachment sequence Arg-Gly-Asp was also noted.

Amino Acid Sequence↗