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)

For comparative studies on the esterase activities of thrombin and trypsin N(alpha)-arylsulfonyl-L-arginine methyl esters were synthetised containing in aromatic ring substituents of different polar nature, size and hydrophobicity. The kinetics of their hydrolysis by thrombin and trypsin were measured. Values of Km and kcat in steady-state conditions were determined. It was shown, that thrombin-catalysed hydrolysis was more sensitive than that of trypsin to the nature of substituents of arylsulfonyl group and determined by their polar and steric effects. A line correlation between specificity constants (kcat/Km) and sigma and Es of substituents were demonstrated. The difference in reactivity of compounds under investigation is suggested to depend on alterations of stability of hydrogen bond between arylsulfonylamide nitrogen atom of substrate and the active center of the enzyme due to changes in the acidity of the arylsulfonylamide group affected by substituent of the benzene ring.
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PMID:[Dependence of thrombin- and trypsin-catalyzed hydrolysis of N-alpha-arylsulfonyl-L-arginine methyl esters on the structure of acylamide part of substrates]. 2 Sep 97

Group I strains of Clostridium botulinum are known to degrade arginine by the arginine deiminase pathway. We have found that C. botulinum Okra B consumed a level of arginine (20 g/liter) higher than the basal requirement for growth (3 g/liter). Arginine was probably the preferred source of nitrogen for biosynthesis but did not serve as a major source of energy. Citrulline and proline were produced as major fermentation products in media containing high levels of arginine, but in media with basal amounts of arginine these products were produced in lower quantities during growth and were later reassimilated. The results indicate that C. botulinum Okra B changes its metabolism during consumption of surplus arginine, and this change is associated with toxin repression, formation of citrulline and proline as end products, and possibly resistance to environmental stresses such as increased acidity and osmolarity.
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PMID:Roles of arginine in growth of Clostridium botulinum Okra B. 163 70

Pure cultures of microorganisms commonly found in supragingival plaque were incubated alone and in combinations to determine the bacterial contribution to the pH-fall-pH-rise that is the central characteristic of the Stephan-curve pH change seen in plaque in vivo after brief exposure to a sugar solution. To avoid the complicating conditions of saliva flow and plaque diffusion, experiments were done with bacterial suspensions in incubations in vitro. In an initial experimental series where each microorganism was incubated only with glucose, all but a few produced the initial pH fall. Some also showed a subsequent small, sharp rise in the pH which then quickly levelled off; this was due to metabolism of endogenous substrate accumulated by most microorganisms during their growth in culture. When arginolytic and non-arginolytic bacteria were each then incubated with both glucose and arginine present (the glucose substrate to stimulate a pH fall and the arginine to stimulate a pH rise), the non-arginolytic gave a progressively more acidic pH response with progressive increase in the cell concentration, whereas the arginolytic bacteria produced a much smaller and variable pH decrease with similar cell concentration increase. Mixing pure cultures of either arginolytic or non-arginolytic bacteria gave acid-base pH responses similar to those of their respective pure cultures, whereas mixing arginolytic with non-arginolytic bacteria resulted in an approximate averaging of their different curves. The organisms present in highest proportion in a mixture had the greatest effects. The outcome of mixing the most numerous streptococcal and actinomyces species found normally in supragingival plaque indicated that the well-established difference in the acidity level of the Stephan pH response of caries-active and caries-inactive plaques could be due to differences in the proportions of their arginolytic and non-arginolytic members.
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PMID:Acid-base pH curves in vitro with mixtures of pure cultures of human oral microorganisms. 267 1

Affinity labeling and comparative sequence analyses have placed Lys-166 of ribulosebisphosphate carboxylase/oxygenase from Rhodospirillum rubrum at the active site. The unusual nucleophilicity and acidity of the epsilon-amino group of Lys 166 (pKa = 7.9) suggest its involvement in catalysis, perhaps as the base that enolizes ribulosebisphosphate (Hartman, F.C., Milanez, S., and Lee, E.H. (1985) J. Biol. Chem. 260, 13968-13975). In attempts to clarify the role of Lys-166 of the carboxylase, we have used site-directed mutagenesis to replace this lysyl residue with glycine, alanine, serine, glutamine, arginine, cysteine, or histidine. All seven of these mutant proteins, purified by immunoaffinity chromatography, are severely deficient in carboxylase activity; the serine mutant, which is the most active, has a kcat only 0.2% that of the wild-type enzyme. Although low, the carboxylase activity displayed by some of the mutant proteins proves that Lys-166 is not required for substrate binding and argues that the detrimental effects brought about by amino acid substitutions at position 166 do not reflect gross conformational changes. As demonstrated by their ability to tightly bind a transition-state analogue (2-carboxyarabinitol 1,5-bisphosphate) in the presence of CO2 and Mg2+, some of the mutant proteins undergo the carbamylation reaction that is required for activation of the wild-type enzyme. Since Lys-166 is required neither for activation (i.e. carbamylation by CO2) nor for substrate binding, it must be essential to catalysis. When viewed within the context of previous related studies, the results of site-directed mutagenesis are entirely consistent with Lys-166 functioning as the base that initiates catalysis by abstracting the C-3 proton from ribulosebisphosphate. An alternative possibility that Lys-166 acts to stabilize a transition state in the reaction pathway cannot be rigorously excluded.
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PMID:Function of Lys-166 of Rhodospirillum rubrum ribulosebisphosphate carboxylase/oxygenase as examined by site-directed mutagenesis. 310 87

1. Bovine neurophysin-II contains 1mol of tyrosine residue/10000g of protein. This residue could be readily nitrated with tetranitromethane. On hydrolysis and amino acid analysis 1mol of 3-nitrotyrosine was found/10000g of protein. Starchgel electrophoresis at pH8.5 showed that nitration had converted the native protein into a single, more acidic species. The increase in acidity was consistent with the observed fall in pK of the tyrosine hydroxyl from 9.2 in native neurophysin to 7.3 in the nitrated protein. Further, the absence of any intermediate species, even under conditions of minimum substitution, confirmed that the molecular weight of the monomer is 10000. 2. O-Acetylation of the tyrosine residue was carried out with N-acetylimidazole, in conjunction with the reversible blocking of amino groups by citraconylation. The degree of O-acetylation, determined spectroscopically, was 0.9mol of O-acetyltyrosine/10000g of protein. 3. The hormone-binding ability of modified protein was tested by equilibrium dialysis and was found to be unchanged by either nitration or O-acetylation of the tyrosine residue. 4. Interaction of neurophysin-II and [8-arginine]-vasopressin gave rise to a characteristic difference spectrum with a peak at 286.8nm and shoulder at 279.6nm. Part of this hyperchromicity is thought to result from entry of the tyrosine residue at position 2 in the hormone into the hydrophobic environment of the binding site. With nitrated neurophysin-II a second peak appeared at 436nm, showing that the tyrosine of the protein is also perturbed. The very large red shift (84nm) in this region suggests that the 3-nitrotyrosyl residue not only enters a more hydrophobic environment on protein-hormone interaction, but is caused to ionize more fully by the approach of some positively charged group.
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PMID:Studies on the chemical modification of the tyrosine residue in bovine neurophysin-II. 546 18

Snake insulin is isolated and crystallized from the pancreas of non-venomous snake (Zaocys dhumnades dhumnades, Cantor). The crystalline form is not rhombohedral but dodecahedral. The primary structure has been determined with the aid of an LKB solid-phase sequencer. In the primary structure of snake insulin, the presence of B5 Arg, B29 Arg, B16 Phe, B25 Tyr and B18 Ile is unusual in comparison with insulins from mammals, birds and fishes. However, the snake insulin we studied is very similar to rattle snake insulin, with the exception that A15 is glutamic acid instead of glutamine and B30 is threonine instead of serine. These differences are consistent with the higher acidity of the snake insulin we studied and with the threonine and serine content in amino acid analysis. The B10 residue of the snake insulin we studied is still histidine. The formation of dodecahedral crystals of the snake insulin has been discussed in connection with the presence of this histidine.
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PMID:The primary structure of snake (Zaocys dhumnades dhumnades, Cantor) insulin. 702 9

Rhodopsin is a member of a family of G protein-coupled receptors which share structural and functional homologies. A tripeptide sequence (Glu or Asp/Arg/Tyr) at the cytoplasmic border of the third transmembrane segment is conserved among most of these receptors. This region is involved in G protein activation in rhodopsin as well as in other receptors. The role of the conserved Glu-134 was studied by site-specific mutagenesis of rhodopsin in combination with a real-time fluorescence assay of G protein (transducin) activation. Assay conditions were chosen under which the transducin activation rate was determined either by rhodopsin-transducin complex formation or by GTP gamma S-induced complex dissociation. Glu-134 was replaced by Gln in order to mimic the protonated state of the carboxylic acid group. This mutation caused the pH dependency of complex formation to extend to the alkaline range as compared with rhodopsin. Replacement of Glu-134 by Asp had an opposite but less pronounced effect on the pH dependency and lowered the overall efficiency of transducin activation. The acidity constant (pKa) of the residue at position 134 did not directly determine the pH sensitivity of complex formation, indicating that other amino acid residues contribute to a titratable binding domain that includes Glu-134. In contrast, the pH sensitivity of GTP gamma S-induced complex dissociation was not changed by the mutations, although absolute rates were affected. The data suggest that the protonated state of Glu-134 favors binding of rhodopsin to transducin and that Glu-134 is not titratable in the rhodopsin-transducin complex.
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PMID:Regulation of the rhodopsin-transducin interaction by a highly conserved carboxylic acid group. 834 12

Enteral nutrition (EN) has several advantages over parenteral nutrition (PN) for postoperative/posttrauma patients. Modern technologies for tube-feeding have made early EN possible. Jejunal tube-feeding has advantages over gastric tube-feeding: faster metabolic recovery, less vomiting, and less risk of regurgitation and aspiration. Immediate or early EN stimulates the splanchnic and hepatic circulations, improves mucosal blood flow, prevents intramucosal acidosis and permeability disturbances, and eliminates the need for stress ulcer prophylaxis. Saliva containing important antimicrobial substances and gastric acidity are important in sepsis prevention. Chewing, saliva, and gastric acidity support gastric nitric oxide (NO) release, important for mucosal blood flow, gastrointestinal (GI) motility, mucus formation, and bacteriostasis. An oral supply of NO-donating substances and chewing of nitrate-rich food, such as lettuce or spinach, can be useful. Oral and mucosa-protective lipids are recommended. H2 blockers and saliva-inhibiting drugs are avoided. Immediate EN should be given, starting with 25 ml/hr and increasing to 100 ml/hr over 24 to 48 hours. For the immunocompromised patient special attention should be given to the purity of water. Bottled water can contain bacteria such as Pseudomonas. Food antioxidants such as glutathione, vitamin E, and beta-carotenes are important. Ingredients for the colonic mucosa are important. Approximately 10% of caloric need is satisfied by so-called colonic food (prebiotics), fermented at the level of the colonic mucosa to produce colonic mucosa nutrients and to prevent gut origin sepsis. More than 10 g of fiber per day is recommended. The fermenting flora (probiotic flora) is deranged owing to disease or antibiotic treatment, and resupply of flora is important. A new concept of ecoimmune nutrition is presented for enteral supply of mucosa-reconditioning ingredients: new surfactants, pseudomucus, fiber, amino acids such as arginine, and mucosa-adhering Lactobacillus plantarum 299.
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PMID:Nutritional support to prevent and treat multiple organ failure. 866 38

It is now generally recognized that cell growth conditions in nature are often suboptimal compared to controlled conditions provided in the laboratory. Natural stresses like starvation and acidity are generated by cell growth itself. Other stresses like temperature or osmotic shock, or oxygen, are imposed by the environment. It is now clear that defense mechanisms to withstand different stresses must be present in all organisms. The exploration of stress responses in lactic acid bacteria has just begun. Several stress response genes have been revealed through homologies with known genes in other organisms. While stress response genes appear to be highly conserved, however, their regulation may not be. Thus, search of the regulation of stress response in lactic acid bacteria may reveal new regulatory circuits. The first part of this report addresses the available information on stress response in Lactococcus lactis. Acid stress response may be particularly important in lactic acid bacteria, whose growth and transition to stationary phase is accompanied by the production of lactic acid, which results in acidification of the media, arrest of cell multiplication, and possible cell death. The second part of this report will focus on progress made in acid stress response, particularly in L. lactis and on factors which may affect its regulation. Acid tolerance is presently under study in L. lactis. Our results with strain MG1363 show that it survives a lethal challenge at pH 4.0 if adapted briefly (5 to 15 minutes) at a pH between 4.5 and 6.5. Adaptation requires protein synthesis, indicating that acid conditions induce expression of newly synthesized genes. These results show that L. lactis possesses an inducible response to acid stress in exponential phase. To identify possible regulatory genes involved in acid stress response, we determined low pH conditions in which MG1363 is unable to grow, and selected at 37 degrees C for transposition insertional mutants which were able to survive. About thirty mutants resistant to low pH conditions were characterized. The interrupted genes were identified by sequence homology with known genes. One insertion interrupts ahrC, the putative regulator of arginine metabolism; possibly, increased arginine catabolism in the mutant produces metabolites which increase the pH. Several other mutations putatively map at some step in the pathway of (p)ppGpp synthesis. Our results suggest that the stringent response pathway, which is involved in starvation and stationary phase survival, may also be implicated in acid pH tolerance.
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PMID:Lactococcus lactis and stress. 887 9

Helicobacter pylori (Hp) is considered as the major pathogen in Hp-associated gastritis but the mechanism of its action has not been fully explained. We investigated both the damaging and protective effects of intragastric (i.g.) application of ammonia (NH4OH) and ammonium ion (NH4Cl), the major products of Hp-derived urease, on the rat stomach with intact and capsaicin-deactivated sensory nerves or suppressed prostaglandin (PG) and nitric oxide (NO) synthesis. NH4OH given i.g. resulted in a concentration-dependent mucosal damage starting at 30 mM and reaching maximum at 250 mM (pH 11), the extent of damage being similar to that obtained with 100% ethanol. NaOH solution (1 mM) at pH 11 given i.g. did not affect mucosal integrity. The damage caused by NH4OH was accompanied by the fall in gastric blood flow (GBF) reaching at 250 mM NH4OH about 30% of the vehicle control value. The NH4OH-induced gastric damage was augmented by capsaicin-induced deactivation of sensory nerves, the suppression of nitric oxide (NO) synthase with L-NAME or the decrease of i.g. acidity by ranitidine. The pretreatment with scavengers of reactive oxidants significantly reduced the area of NH4OH-induced gastric lesions. When the mucosa was first exposed to a low 15-mM concentration of NH4OH and then insulted with large 250 mM NH4OH or with 100% ethanol, the lesion area was markedly reduced as compared to that obtained with 250 mM NH4OH or 100% ethanol alone. This adaptive protection by 'mild' concentration of NH4OH against strong irritants (250 mM NH4OH or 100% ethanol) was reversed, in part, by pretreatment with L-NAME and indomethacin. NH4Cl (60-500 mM) given i.g. alone failed to affect the mucosal integrity but when applied before 100% ethanol it produced a concentration-dependent fall in the mucosal damage by these irritants. We conclude that; (1) ammonia at higher concentrations damages the gastric mucosa, while ammonium ion exerts the protective activity; (2) the ammonia-induced gastric damage may involve the formation of reactive oxidants; (3) ammonia at lower concentration acts like a mild irritant via the activation of sensory nerves, NO-arginine pathway and PG.
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PMID:Gastric mucosal damage and adaptive protection by ammonia and ammonium ion in rats. 891 6


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