Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three tobacco cell lines have been analyzed which are resistant to lethal inhibitors of either putrescine production or conversion of putrescine into polyamines. Free and conjugated putrescine pools, the enzymic activities (arginine, ornithine, and S-adenosylmethionine decarboxylases), and the growth characteristics during acidic stress were measured in suspension cultures of each cell line. One cell line, resistant to difluoromethylornithine (Dfr1) had a very low level of ornithine decarboxylase activity which was half insensitive to the inhibitor in vitro. Intracellular free putrescine in Dfr1 was elevated 10-fold which was apparently due to a 20-fold increase in the arginine decarboxylase activity. The increased free putrescine titer was not reflected in an increased level of spermidine, spermine, or putrescine conjugation. Dfr1 cultures survived acidic stress at molarities which were lethal to wild type cultures. Two other mutants, resistant to methylglyoxal bis(guanylhydrazone) (Mgr3, Mgr12), had near normal levels of the three decarboxylases and normal titers of free putrescine, spermidine, and spermine. Both mutants however had elevated levels of conjugated putrescine. Mgr12 had an increased sensitivity to acidic medium. These results suggest that increased levels of free putrescine production may enhance the ability of tobacco cells to survive acid stress. This was supported by the observation that cytotoxic effects of inhibiting arginine decarboxylase in wild type cell lines were dependent on the acidity of the medium.
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PMID:Utilization of putrescine in tobacco cell lines resistant to inhibitors of polyamine synthesis. 1666 27

The molecular recognition of adenosine-5'-triphosphate (ATP) with L-arginine (Arg) through hydrogen bonding interactions has been found using 1H NMR, H-H NOESY, acidity titration and fluorescence spectra techniques. The interactions could influence charge distribution in Arg and induce Arg conformational variation. It is realized that Arg conformation change from a partly folded state to an extended state through the rotation of CC single bonds of Arg side chain during the molecular recognition process.
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PMID:Influence of hydrogen bonds on charge distribution and conformation of L-arginine. 1704 18

The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad - Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase inhibitor; N-nitro-L-arginine methyl ester (L-NAME) and when nitric oxide was in excess by administration of exogenous NO donor, sodium nitroprusside (SNP). Histamine or carbachol increased acid secretion in the toad. Acid output increased from 0.32 +/- 0.04 mEq/15min to 0.56 +/- 0.08 and 0.61 +/- 0.05 mEq/15min for histamine and carbachol respectively [P < 0.05]. Pretreatment of the toad with L-NAME produced further increases in histamine (0.62 +/- 0.06 mEq/15min) or carbachol (0.74 +/- 0.06 mEq/15min) induced acid secretion respectively. SNP however, completely abolished the acid secretion stimulated by either histamine or carbachol. It was therefore concluded that nitric oxide has a negative influence on the histamine or carbachol-stimulated acid secretion in the toad - Bufo regularis.
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PMID:Influence of nitric oxide on histamine and carbachol-induced gastric Acid secretion in the common african toad - bufo regularis. 1722 Sep 32

The guaianolide type sesquiterpene lactones chlorojanerin, 13-acetyl solstitialin A and solstitialin A were identified as the anti-ulcerogenic components of the chloroform extract of the aerial parts of Centaurea solstitialis ssp. solstitialis (Asteraceae). In this study, these compounds were investigated by using various in vivo ulcer models in rats and mice. Chlorojanerin was shown to be significantly effective in preventing the induction of lesions by ethanol- (EtOH-) (both oral and subcutaneous administration), indomethacin-, indomethacin plus HCl/EtOH-, N(G)-nitro-l-arginine methyl ester plus EtOH-, N-ethylmaleimide plus EtOH-, water immersion and restraint stress, and serotonin, as well as inhibiting titratable gastric acidity and acid output, and increasing gastric pH, but was ineffective in the prevention of ulcers induced by pyloric ligation, diethyldithiocarbamate, and cysteamine, and had no effect on gastric secretion volume or peptic activity. A mixture of 13-acetyl solstitialin A (95%) and solstitialin A (5%) was found to be significantly effective against EtOH-induced lesions on oral administration but was ineffective when administered subcutaneously. This mixture was also found to be effective in preventing lesions induced by EtOH, indomethacin, indomethacin plus HCl/EtOH, N(G)-nitro-l-arginine methyl ester plus EtOH, N-ethylmaleimide plus EtOH, water immersion and restraint stress, serotonin and cysteamine, as well as inhibiting titratable gastric acidity and titratable acid output, and gastric pH, but was found ineffective against the pyloric ligation-induced and diethyldithiocarbamate-induced ulcerogenesis models, as well as gastric secretion volume and peptic activity. On the other hand, active compounds did not show any toxic effect on acute toxicity (3 days administration) evaluation tests in mice.
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PMID:Evaluation of the anti-ulcerogenic effect of sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis by using various in vivo and biochemical techniques. 1741 88

The YUH1 gene coding for ubiquitin C-terminal hydrolase 1, a deubiquitinating enzyme, was cloned from the Saccharomyces cerevisiae genomic DNA and expressed in Escherichia coli. YUH1 was fused with the 6 histidine tag at the N-terminus (H6YUH1) or C-terminus (YUH1H6) and purified by an immobilized metal affinity chromatography with high purity. By using a fluorogenic substrate, Z-Arg-Leu-Arg-Gly-Gly-AMC, the deubiquitinating activities for H6YUH1 (1.72U/mg) and YUH1H6 (1.61U/mg) were about 18 times higher than 0.092U/mg for H6UBP1, ubiquitin specific protease 1 of S. cerevisiae containing the 6 histidine residue at the N-terminus which is normally used in protein engineering. YUH1 had the optimal temperature of 27 degrees C and acidity of pH 8.5. Analysis of thermal deactivation kinetics of H6YUH1 estimated 3.2 and 1.4h of half lives at 4 and 52 degrees C, respectively. Immobilization onto the Ni-NTA affinity resin and environmental modulation were carried out to improve the stability of YUH1. Incubation of the immobilized YUH1 in 50% glycerol solution at -20 degrees C resulted in 52% of decrease in specific activity for 7days, corresponding to a 2.7-fold increase compared with that of the free YUH1 incubated in the same solution at 4 degrees C.
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PMID:Characterization of ubiquitin C-terminal hydrolase 1 (YUH1) from Saccharomyces cerevisiae expressed in recombinant Escherichia coli. 1770 60

cDNA for octopine dehydrogenase (ODH) from the adductor muscle of the great scallop, Pecten maximus, was cloned using 5'- and 3'-RACE. The cDNA comprises an ORF of 1197 nucleotides and the deduced amino acid sequence encodes a protein of 399 amino acids. ODH was heterologously expressed in Escherichia coli with a C-terminal penta His-tag. ODH-5His was purified to homogeneity using metal-chelate affinity chromatography and Sephadex G-100 gel filtration. Recombinant ODH had kinetic properties similar to those of wild-type ODH isolated from the scallop's adductor muscle. Site-directed mutagenesis was used to elucidate the involvement of several amino acid residues for the reaction catalyzed by ODH. Cys148, which is conserved in all opine dehydrogenases known to date, was converted to serine or alanine, showing that this residue is not intrinsically important for catalysis. His212, Arg324 and Asp329, which are also conserved in all known opine dehydrogenase sequences, were subjected to site-directed mutagenesis. Modification of these residues revealed their importance for the catalytic activity of the enzyme. Conversion of each of these residues to alanine resulted in strong increases in K(m) and decreases in k(cat) values for pyruvate and L-arginine, but had little effect on the K(m) and k(cat) values for NADH. Assuming a similar structure for ODH compared with the only available structure of a bacterial opine dehydrogenase, these three amino acids may function as a catalytic triad in ODH similar to that found in lactate dehydrogenase or malate dehydrogenase. The carboxyl group of pyruvate is then stabilized by Arg324. In addition to orienting the substrate, His212 will act as an acid-base catalyst by donating a proton to the carbonyl group of pyruvate. The acidity of this histidine is further increased by the proximity of Asp329.
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PMID:Putative reaction mechanism of heterologously expressed octopine dehydrogenase from the great scallop, Pecten maximus (L). 1802 27

Electrostatic interactions in proteins can be probed experimentally through determination of residue-specific acidity constants. We describe here triple-resonance NMR techniques for direct determination of lysine and arginine side-chain protonation states in proteins. The experiments are based on detection of nonexchangeable protons over the full range of pH and temperature and therefore are well suited for pKa determination of individual amino acid side chains. The experiments follow the side-chain 15Nzeta (lysine) and 15Nepsilon or 13Czeta (arginine) chemical shift, which changes due to sizable changes in the heteronuclear electron distribution upon (de)protonation. Since heteronuclear chemical shifts are overwhelmed by the charge state of the amino acid side chain itself, these methods supersede 1H-based NMR in terms of accuracy, sensitivity, and selectivity. Moreover, the 15Nzeta and 15Nepsilon nuclei may be used to probe changes in the local electrostatic environment. Applications to three proteins are described: apo calmodulin, calbindin D9k, and FKBP12. For apo calmodulin, residue-specific pKa values of lysine side chains were determined to fall between 10.7 and 11.2 as a result of the high net negative charge on the protein surface. Ideal two-state titration behavior observed for all lysines indicates the absence of significant direct charge interactions between the basic residues. These results are compared with earlier studies based on chemical modification.
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PMID:Residue-specific pKa determination of lysine and arginine side chains by indirect 15N and 13C NMR spectroscopy: application to apo calmodulin. 1804 88

The gastroprotective mechanism of the natural diterpene ferruginol was assessed in mice and rats. The involvement of gastric prostaglandins (PGE(2)), reduced glutathione, nitric oxide or capsaicin receptors was evaluated in mice either treated or untreated with indometacin, N-ethylmaleimide (NEM), N-nitro-L-arginine methyl ester (L-NAME) or ruthenium red, respectively, and then orally treated with ferruginol or vehicle. Gastric lesions were induced by oral administration of ethanol. The effects of ferruginol on the parameters of gastric secretion were assessed in pylorus-ligated rats. Gastric PGE(2) content was determined in rats treated with ferruginol and/or indometacin. The reduction of gastric glutathione (GSH) content was determined in rats treated with ethanol after oral administration of ferruginol, lansoprazole or vehicle. Finally, the acute oral toxicity was assessed in mice. Indometacin reversed the gastroprotective effect of ferruginol (25 mg kg(-1)) but not NEM, ruthenium red or L-NAME. The diterpene (25 mg kg(-1)) increased the gastric juice volume and its pH value, and reduced the titrable acidity but was devoid of effect on the gastric mucus content. Ferruginol (25, 50 mg kg(-1)) increased gastric PGE(2) content in a dose-dependent manner and prevented the reduction in GSH observed due to ethanol-induced gastric lesions in rats. Single oral doses up to 3 g kg(-1) ferruginol did not elicit mortality or acute toxic effects in mice. Our results showed that ferruginol acted as a gastroprotective agent stimulating the gastric PGE(2) synthesis, reducing the gastric acid output and improving the antioxidant capacity of the gastric mucosa by maintaining the GSH levels.
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PMID:Gastroprotective activity of ferruginol in mice and rats: effects on gastric secretion, endogenous prostaglandins and non-protein sulfhydryls. 1823 73

The uptake of L-arginine into mouse peritoneal macrophages can be inhibited by numerous amino acids and derivatives. Kinetic studies showed an almost entirely competitive inhibition for both cationic and neutral amino acids and derivatives suggesting that the comparison of their binding specificity by using a quantitative structure-activity relationship (QSAR) study is reasonable. The properties of the most efficient inhibitors were the following: the length of the aliphatic side chain, a general structural similarity to L-arginine (>0.79), cationic character, L-configuration, the presence of an alpha-amino group (with a mean pK(a) of 9.41), the van der Waals volume (mean 225 A(3)) and a low logP value (mean: -2.99). The significance of four other descriptors (neutral character, presence and the pK(a) of an alpha-carboxyl group, and the presence of a modified guanidino group) is much lower. Similar results were obtained for the hCAT-1 cell line, but the significance of the descriptors was slightly different. The L-configuration, van der Waals volume, the low logP value and the length of aliphatic side chain were the most significant, while the pK(a) value of the side chain (mean pK(a)=11.6) was found to be more important than that of the alpha-amino group. In addition, the general similarity to L-arginine, the presence of an amino group in the terminal position of the side chain (Orn, Lys) and the basic character were significant descriptors, while the significance of the acidity is negligibly low. As a final conclusion, the following descriptors were found to be important generally for the cationic transporters: the van der Waals volume, hydrophobicity (log P); L-configuration; the size of the side chain; the general similarity to L-arginine; the presence of an alpha-amino group; the general basicity of the molecule; the pK(a) values of the alpha-amino group (in macrophages) or that of the side chain (in CAT-1 cells). These descriptors can be regarded as the general structurally important binding characteristics of the cationic amino transporters.
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PMID:Binding specificity of the L-arginine transport systems in mouse macrophages and human cells overexpressing the cationic amino acid transporter hCAT-1. 1850 24

Singly hydrated clusters of deprotonated amino acids were studied using an electrospray high-pressure mass spectrometer equipped with a pulsed ion-beam reaction chamber. Thermochemical data, DeltaH(o), DeltaS(o), and DeltaG(o), for the hydration reaction [AA - H](-) + H(2)O = [AA - H](-).(H(2)O) were obtained from gas-phase equilibria determinations for AA = Gly, Ala, Val, Pro, Phe, Lys, Met, Trp, Gln, Arg, and Asp. The hydration free-energy changes are found to depend significantly on the side-chain substituents. The water binding energy in [AA - H](-).(H(2)O) increases with the gas-phase acidity of AA. The anionic hydrogen bond strengths in [AA - H](-).(H(2)O) are compared with those of the cationic bonds in the corresponding AAH(+).(H(2)O) systems.
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PMID:Hydration energies of deprotonated amino acids from gas phase equilibria measurements. 1855 12


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