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)

Four genetic variants of alcohol dehydrogenase from Drosophila melanogaster have been examined: wild-type F-enzyme (from the AdhF strain), the D-type mutant form (from the AdhD strain), which is catalytically active, and two proteins lacking enzymic activity (from the Adhn11 and Adhn5 strains). The proteins were compared by mapping of tryptic peptides. One pair of difference peptides was seen in the comparisons of the D and F-type enzymes. These peptides were purified and their sequences determined. The difference between the two proteins was shown to be an exchange at a single position of glycine in the F for glutamic acid in the D-type protein. This exchange is consistent with the greater acidity of alcohol dehydrogenase from the AdhD strain and can be produced by a single base mutation. The difference between the n11 and F-type proteins was not detected and is suggested to be in a large tryptic peptide. In addition to the difference peptides, other fragments from Drosophila alcohol dehydrogenase were isolated and analyzed. The sequences determined account for approximately 50% of the amino acids in the protein and include regions around the two cysteine residues as well as possible terminal structures. All peptides analyzed were examined for structural identities with horse and yeast alcohol dehydrogenases. No clearly significant similarities were seen between the Drosophila enzyme and the other two proteins but low degrees of homology are possible. From the variations in cysteine-containing regions large differences appear to exist between the active sites of the insect enzyme and the other alcohol dehydrogenases.
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PMID:Structural analyses of mutant and wild-type alcohol dehydrogenases from drosophila melanogaster. 82 18

Seeds of African locust bean, melon, castor oil bean and soybean were processed and fermented for 3 days to produce local condiments in the laboratory with a method that simulated the traditional production process. Microorganisms associated with their fermentation and the organoleptic properties of the products were compared. Altogether, seven species of bacteria were involved in the fermentation. These included five Bacillus spp. and one species each of Pseudomonas and Staphylococcus. Their occurrence vary between the seeds on the different days of fermentation. However, Bacillus spp. were present in all the seeds throughout the fermentation period. The sensory evaluation preference rating for the four products was highest for soybean condiment, followed by that made from locust bean. Melon condiment was the least preferred among the four products. Statistical analysis showed that there were significant differences (P less than or equal to 0.05) among the four products for each of the four organoleptic properties evaluated by the judges and also for titratable acidity. Glutamic acid level of soybean condiment was highest (0.31%) among the four products with that of melon being the lowest (0.04%). These results could serve as useful indices for the development of starter culture and optimization of production process in commercializing the production of these local condiments.
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PMID:Comparative study of microorganisms and sensory attributes of condiments from the fermentation of different seeds. 167 37

Effects of food and gastric acidity on the bioavailability of ketoconazole tablets were investigated in 12 volunteers using a six-treatment, randomized, Latin-square crossover design. All volunteers received all treatments, as follows: (A) ketoconazole 200 mg administered after a fast; (B) ketoconazole 200 mg with a standardized high-fat meal; (C) ketoconazole 200 mg with a standardized high-carbohydrate meal; (D) ketoconazole 200 mg after pretreatment with glutamic acid hydrochloride 680 mg as capsules; (E) ketoconazole 200 mg in a simulated achlorhydric state induced with cimetidine and sodium bicarbonate; and (F) ketoconazole 200 mg administered with glutamic acid hydrochloride in a simulated achlorhydric state. Ketoconazole concentrations were measured by high-performance liquid chromatography in plasma samples drawn immediately before and at various times over 24 hours after drug administration. Bioavailability variables, including natural logarithm transformation for area under the concentration-time curve (AUC), were subjected to analysis of variance followed by Duncan's Multiple Range testing. Treatments B and C significantly prolonged the times required to achieve the peak plasma ketoconazole concentration, and treatment C also significantly reduced the peak plasma ketoconazole concentration (Cmax) compared with treatment A. There was a trend toward increased AUC values with treatment B and decreased AUC values with treatment C. Treatment D produced a higher Cmax compared with treatment A, and treatment E produced large, significant reductions in Cmax and AUC values compared with treatment A. Treatment F significantly increased AUC values and Cmax compared with treatment E.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of food and gastric acidity on absorption of orally administered ketoconazole. 335 20

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

To investigate the role of acidic and phosphorylated amino acids in the function of the major transactivation domain (tau 1) of the glucocorticoid receptor, we have performed a mutagenesis study. Aspartic and glutamic acid residues were neutralized in clusters of 2 to 4 amino acids throughout the tau 1 domain. The activity of the mutant proteins was determined using transactivation assays in yeast and mammalian cells. Some acidic residues in the core region of tau 1 appear to play a minor role in tau 1 activity, but, generally, individual acidic residues are not critical for activity. Mutagenesis of five serine residues that are phosphorylated in the mouse glucocorticoid receptor and which are conserved in the human receptor did not affect the transactivation activity of the tau 1 domain in yeast. As in mouse cells, these serine residues are the predominant sites of phosphorylation for ectopically expressed receptor in yeast, since the mutant protein lacking all five sites had a severely reduced phosphorylation level. Mutant proteins in which larger numbers of acidic residues are neutralized show a progressive decrease in activity indicating that acidity in general is important for tau 1 function. However, our results are not consistent with the "acid blob" theory of transactivator function that has been suggested for some other activator proteins. Other putative roles for the acidity of tau 1 are discussed.
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PMID:Role of acidic and phosphorylated residues in gene activation by the glucocorticoid receptor. 761 59

Monoclonal antibodies (mAbs) were derived against the procyclic culture form of Trypanosoma congolense and 14 were selected which bound to the surface of living procyclics in immunofluorescence assays. These antibodies bound to procyclics and epimastigotes of T. congolense (both savannah-type and Kilifi-type) and procyclics of Trypanosoma simiae, but not to procyclics of other species of trypanosomes, to bloodstream forms of several species of trypanosomes or to Leishmania, and were thus life cycle stage- and subgenus-specific. Fluorescence-activated cell sorter analysis with these antibodies showed that the kinetics of expression of the surface antigen during transformation from bloodstream to procyclic forms was similar to that of procyclin or procyclic acidic repetitive protein (PARP) of T. brucei spp. appearing at the cell surface as early as 8 h after initiating transformation. All fourteen antibodies detected broad bands of 40-44 and 28-32 kDa in immunoblot analysis of whole procyclic lysates and were specific for carbohydrate epitopes. The antigen was purified by cation-exchange chromatography and gel electrophoresis, and was shown to be an acidic glycoprotein. Amino acid microanalysis of the purified antigen showed an abundance of glutamic acid/glutamine and alanine. Sequences of peptides produced by cyanogen bromide cleavage matched amino acid sequences predicted by the nucleotide sequence of a gene described in the accompanying paper by Bayne et al. [26]. No sequence similarity to T. brucei procyclin/PARP or to any other protein was found. However, its stage and subgenus specificity, surface disposition, immunodominance, acidity and kinetics of expression during transformation from bloodstream to procyclic forms indicate that the molecule is an analog of procyclin/PARP described in T. brucei spp.
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PMID:Identification and characterization of an acidic major surface glycoprotein from procyclic stage Trypanosoma congolense. 790 27

In healthy volunteers, the bioavailability of ketoconazole is significantly decreased during simultaneous administration with sucralfate. In an effort to address this problem, we examined the interaction between sucralfate and ketoconazole in aqueous solutions and in simulated gastric fluid (SGF) at various initial pHs (1, 2, 3, and 6) in the presence or absence of glutamic acid hydrochloride (GA). Samples from each solution were taken 30 min and 2 h after the addition of ketoconazole to evaluate the solubility of ketoconazole over the usual time period of maximal absorption of ketoconazole in humans. The addition of GA to SGF leads to an increase in solution acidity, while the pHs of SGF at a pH of 1, 2, or 3 are markedly increased by the addition of sucralfate. There is a net decrease in acidity from initial pHs for the pH 1, 2, and 3 solutions when GA and sucralfate are combined. The concentration of ketoconazole in SGF at pHs of 1, 2, 3, 4, and 6 was evaluated in order to assess the pH-dependent solubility properties of the drug in the absence of other interacting species. Regardless of the initial pH, combinations of GA plus ketoconazole showed high concentrations of ketoconazole (approximately 100%) in solution. In contrast, significant decreases in the concentration of soluble ketoconazole were observed when sucralfate was mixed with ketoconazole, and, in some cases, soluble ketoconazole was not detectable. The addition of GA to a mixture of sucralfate and ketoconazole leads to a significant increase in the concentration of solubilized ketoconazole. Nonetheless, important sucralfate-ketoconazole interactions are still observed. After 2 h, approximately 35% of the maximal ketoconazole concentration remained in solution. Comparison of the ketoconazole concentrations at different pHs with the predicted concentrations of the three protonation species of ketoconazole [H2(ketoconazole)(2+), H(ketoconazole)(+), or ketoconazole] showed no correlation. Therefore, the decrease in ketoconazole solubility is not simply a reflection of pH perturbation associated with the dissolution of sucralfate. The observed data are most consistent with a model that has H2(ketoconazole)(2+) or H(ketoconazole)(+) forming an electrostatic interaction with the sucralfate polyanion. The findings of this study suggest that the coadministration of sucralfate with other azole antifungal agents should be investigated.
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PMID:In vitro analysis of the interaction between sucralfate and ketoconazole. 791 Jul 23

The STP-C488 oncogene of herpesvirus saimiri has transforming activity independent of the rest of the viral genome. Three distinct structural regions can be predicted from the STP-C488 sequence: an acidic amino terminal domain, a collagen domain, and a hydrophobic carboxyl-terminal domain. To study the importance and functional roles of these regions, 25 different mutant forms of STP-C488 were generated. Net negative charge in the 17 amino acid amino-terminal domain was found to be important for protein structure and transformation. Increasing the net negative charge decreased electrophoretic mobility and decreasing net negative charge increased electrophoretic mobility. The three glutamic acid residues and overall acidity in this region were found to be necessary to retain potent transforming activity. Interruption of the 18 collagen-like repeats in the central region also interrupted transforming activity. The hydrophobic region at the carboxyl terminus was found to be important for membrane localization. The acidic amino-terminal domain is likely to be the catalytic or ligand binding site of STP-C488.
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PMID:Distinct functional domains of STP-C488 of herpesvirus saimiri. 794 43

In a randomized crossover trial, gastric acidity and gastric microbial colonization in 19 men infected with human immunodeficiency virus (HIV) (of whom nine had AIDS) were assessed. Gastric acidity was assessed during a baseline period and following pentagastrin or glutamic acid administration. Only two (22.2%) of the nine patients with AIDS and none of the non-AIDS patients were hypochlorhydric, as determined by maximal acid output. However, 60% and 67% of patients in the HIV-infected and AIDS groups, respectively, had persistently elevated gastric pH values during the baseline period. Both pentagastrin and glutamic acid significantly increased gastric acidity. Gastric colonization with Candida albicans and gram-positive mouth flora was common. Overall, this study demonstrates that many HIV-infected patients have elevated gastric pH values that may lead to alteration in drug absorption. The large degree of intrasubject and intersubject variability observed in gastric pH suggests that, unfortunately, one cannot predict which patients will have elevated gastric pH values.
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PMID:Alterations in gastric acidity in patients infected with human immunodeficiency virus. 874 28

The objective of the present experiments was to study some properties of fowl spermatozoa which may play a role in the sperm storage and emptying mechanism of the uterovaginal sperm storage tubules (SST) of the hen. The effects exerted by different amino acids (aspartic acid, Asp; glutamic acid, Glu; gamma-aminobutyric acid, GABA; glycine, Gly) and by the pH of the environment at 24 and 39 degrees C on the motility and agglutination of cock spermatozoa were studied in vitro. The spermatozoa did not show agglutination in the presence of Asp and Glu, and became immobilised if the concentration of Glu or the acidity of the environment was increased. In neutral solutions of GABA and Gly or in a faintly alkaline solution characteristic plait-like conglomerations could be seen. The motility of spermatozoa immobilised by Glu could be restored in a varying degree by the addition of GABA or Gly. At a temperature of 24 degrees C, the spermatozoa became immobilised in a medium of pH 6.0 while showed maximum motility at pH 7.1. At 39 degrees C, the spermatozoa were immobilised at higher pH (6.2) and required a pH value as high as 7.4-7.5 to show the highest motility. Spermatozoa inactivated in an acidic solution could be immediately mobilised by alkalisation of the medium, irrespective of the Ca2+ content of the solution. Thus, Ca2+ was not found to play a role in the reactivation of spermatozoa. Nevertheless, marked differences were observed in the maintenance of sperm motility between solutions either containing or lacking Ca2+. As the concentration changes of the above-mentioned amino acids and the pH changes were found to affect the motility and agglutination of spermatozoa in vitro, they may influence also the regulatory mechanism of the uterovaginal SST during the egg-formation cycle in vivo.
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PMID:Motility and agglutination of fowl spermatozoa in media of different amino acid content and pH value in vitro. 890 46


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