Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid and pepsin have been designated the "aggressive factors" in peptic ulcer because they are essential for ulcer formation and because a reduction in their luminal concentrations is usually followed by ulcer healing. Acid enables peptic aggression by converting pepsinogen to pepsin, by providing the highly acidic pH required for pepsin activity, and by denaturing proteins, thereby increasing their susceptibility to the action of pepsin. Pepsin causes peptic aggression by hydrolyzing peptide linkages which bind together the constituent amino acids of proteins. The first step in this reaction is the formation of a complex between the active site of pepsin and the protein substrate. Sucralfate, which is the basic aluminum salt of sucrose octasulfate, inhibits this step by forming an electrostatic complex with proteins. As such, sucralfate inhibits peptic aggression without decreasing acid-pepsinogen secretion or raising intragastric pH. Because of its affinity for proteins and its insolubility and inherent viscosity in acid, sucralfate forms a physical coating over the ulcer crater. This coating further inhibits peptic aggression by producing a barrier to the diffusion of acid and pepsin. Additionally, the basic aluminum moieties of sucralfate may serve to buffer hydrogen ions as they attempt to permeate the viscous layer. The sum of these effects appears to explain the ability of sucralfate to accelerate the rate of healing of peptic ulcer.
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PMID:Inhibition of peptic aggression by sucralfate. The view from the ulcer crater. 641 6

A simplification of the traditional hemoglobin methods for determining serum pepsinogen concentration was developed. In this method, 10% trichloroacetic acid solution was added to control samples, and hemoglobin substrate was added to controls and active enzyme samples; standards and samples were incubated for 18 hours, the proteins in the active tubes were precipitated with trichloroacetic acid and removed by filtration, and the absorbances of the supernatant of each standard and sample at 280 nm were measured. The major differences between this method and other methods for determining pepsinogen values are that the preacidification of serum with hydrochloric acid was eliminated, the incubation period was reduced to 18 hours (down from 24 hours), the relative pepsinogen concentration was determined by measuring the concentration of hydrolysis products, using ultraviolet, rather than visible absorbance, and a pepsin standard curve was used to determine the serum pepsinogen concentration. Comparison of freshly prepared pepsinogen and pepsin standard curves indicated that the pepsinogen preparations were slightly more active than the pepsin preparations (on a weight-to-weight basis) on the same substrate. Pepsin standards are used because they are more stable than pepsinogen standards. Three linear standard curve ranges were used: O 10 to 100, 50 to 300, and 100 to 500 ng of pepsinogen/ml of serum. The use of pepsin standard curves permits some variability of the incubation conditions without altering the results. For best results, the hemoglobin substrate solution should be prepared daily. This method may be useful in diagnosing ostertagiasis.
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PMID:Method for determining serum pepsinogen concentration, using pepsin standards and ultraviolet absorbance. 680 72

Porcine pepsinogen B was prepared from extracts of adult porcine fundic mucosa. Immunoelectrophoresis showed no immunochemical cross-reactions between pepsinogen B and other porcine gastric zymogens. Pepsin B was purified after activation of the zymogen. The enzyme showed an optimum of general proteolytic activity at pH 3.0. Activation of pepsinogen B at pH 2 resulted in formation of the covalent intermediate (pseudo-pepsin B) by proteolytic cleavage of bond Met16p-Glu17p (pig pepsinogen A numbering, "p" indicates residues of the prosegment peptide). Pseudopepsin B was stable at pH 2. The intermediate was converted to pepsin B at pH 5.5. The overall activation of pepsinogen B was much slower than found for other investigated gastric zymogens. During the conversion of pepsinogen B to mature pepsin B a segment of 43 amino acid residues was cleaved from the N-terminal of pepsinogen B. The amino acid sequence of the prosegment and the first 24 residues of pepsin B was determined. Relative to porcine pepsinogen A, progastricsin, and prochymosin, the following degrees of identities were observed: 40, 55, and 51%.
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PMID:Purification and characterization of porcine pepsinogen B and pepsin B. 757 16

Twelve healthy volunteers (6 females, 6 males) between 26 and 36 years of age were enroled in this double-blind, randomized, placebo-controlled, three-way cross-over study. The objective was to determine the influence of lansoprazole (Agopton, Takeda Pharma GmbH, Aachen), a novel proton pump inhibitor, in doses of 30 and 60 mg, on the intragastric pH, on meal-stimulated gastric acid secretion and on the concentration of gastrointestinal hormones and enzymes in serum and gastric juice. Active drug or placebo had to be taken as single daily morning doses on an empty stomach for 7 days. Each wash-out period between drug application periods was 2 weeks long. Lansoprazole induced a dose-related increase in intragastric pH as well as a relevant reduction of basal acid output, meal-stimulated acid output and meal-stimulated secretion volume. 60 mg lansoprazole was significantly superior to 30 mg in increasing intragastric pH. The basal secretion volume in volunteers on 30 and 60 mg lansoprazole were lower than in volunteers on placebo. Serum gastrin and serum pepsinogen concentrations increased in a dose-dependent manner. Pepsin output and pepsin activity in gastric juice were slightly decreased in volunteers on 30 mg lansoprazole and markedly suppressed in volunteers on 60 mg lansoprazole 2 h after meal stimulation. Intrinsic factor concentration increased in volunteers on lansoprazole with a clear dose relationship. The evaluation of laboratory data and reported nonserious adverse events proved the relative safety of this new antiulcer agent.
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PMID:Influence of lansoprazole on intragastric 24-hour pH, meal-stimulated gastric acid secretion, and concentrations of gastrointestinal hormones and enzymes in serum and gastric juice in healthy volunteers. 775 Jun 67

To verify the effect of age on gastric secretions in gastric (GU) and duodenal ulcer (DU) patients, we carried out a retrospective study evaluating basal and stimulated gastric acid secretion in 427 peptic ulcer subjects aged between 12 and 73 years (GU = 74, DU = 353) in addition to studying gastric juice pepsin, serum pepsinogen group A (PGA) and gastrin in 175 patients (GU = 28, DU = 147). All subjects were then divided into groups according to their sex and age (< 30, 30-39, 40-49, 50-59 and > 60 years). Basal, maximal and peak acid outputs (BAO, MAO, PAO) were unchanged in the various age groups, though MAO and PAO were higher in males than females and in DU than in those with GU, even in the elderly (> 60 years). Pepsin and gastrin levels were unchanged at the various ages in GU and DU, while PGA was higher in males with DU aged 50 or over. This demonstrates that acid, pepsin and gastrin secretions do not change with age in ulcer patients. Acid secretion retains its typical distribution according to pathology (DU > GU) and sex (males > females), and also appears to have a fundamental pathogenetic role in peptic ulcer in the elderly.
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PMID:Effect of age on gastric acid, pepsin, pepsinogen group A and gastrin secretion in peptic ulcer patients. 795 81

Pepsin contains, in a single chain, two conformationally homologous lobes that are thought to have been evolutionarily derived by gene duplication and fusion. We have demonstrated that the individual recombinant lobes are capable of independent folding and reconstitution into a two-chain pepsin or a two-chain pepsinogen (Lin, X., et al., 1992, J. Biol. Chem. 267, 17257-17263). Pepsin spontaneously inactivates in neutral or alkaline solutions. We have shown in this study that the enzymic activity of the alkaline-inactivated pepsin was regenerated by the addition of the recombinant N-terminal lobe but not by the C-terminal lobe. These results indicate that alkaline inactivation of pepsin is due to a selective denaturation of its N-terminal lobe. A complex between recombinant N-terminal lobe of pepsinogen and alkaline-denatured pepsin has been isolated. This complex is structurally similar to a two-chain pepsinogen, but it contains an extension of a denatured pepsin N-terminal lobe. Acidification of the complex is accompanied by a cleavage in the pro region and proteolysis of the denatured N-terminal lobe. The structural components that are responsible for the alkaline instability of the N-terminal lobe are likely to be carboxyl groups with abnormally high pKa values. The electrostatic potentials of 23 net carboxyl groups in the N-terminal domain (as compared to 19 in the C-terminal domain) of pepsin were calculated based on the energetics of interacting charges in the tertiary structure of the domain. The groups most probably causing the alkaline denaturation are Asp11, Asp159, Glu4, Glu13, and Asp118.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conformational instability of the N- and C-terminal lobes of porcine pepsin in neutral and alkaline solutions. 840 Dec 24

Peptides from a Staphylococcus aureus (V8) proteinase digest of human pepsin 3b have been identified by amino acid sequence analysis. Only 137 out of 326 expected residues were detected from the C and N terminal regions of the molecule. Comparison with amino acid sequences derived from nucleotide analysis of three different pepsinogen A genes, identified 2 out of 4 possible substitutions. The presence of valine at position 30 and leucine at 291 indicates that the major pepsin component of gastric juice, pepsin 3b, corresponds to pepsinogen genotype PGA-3. Reversed-phase chromatography of native human pepsin 3b on C4 (300 A), C18 (300 A) or polymer (1000 A) columns was optimal on the C4 column and gradient elution with 2-propanol rather than acetonitrile. Denaturation of the protein in guanidinium hydrochloride, urea or high pH resulted in irreversible column retention. The marked hydrophobicity of denatured pepsin 3b may thus explain why the central segment of the protein was not revealed by peptide map analysis.
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PMID:Human pepsin 3b peptide map sequence analysis, genotype and hydrophobic nature. 840 29

To study the effect of Esaprazole, a new antiulcer drug, on acid, peptic and alkaline secretion a modified gastric acid test was performed in 18 duodenal ulcer patients. Pentagastrin was administered as bolus 30' and 75' after the beginning of the test, followed by Esaprazole 300 mg i.v. at 90'. Gastric juice was collected every 15' for determination of: total volume, volume of non parietal secretion, acid, bicarbonate and pepsin output. Serum pepsinogen group I was determined by radioimmunoassay. Esaprazole had a significant inhibitory effect on the total volume of gastric secretion and on volume of non parietal secretion. Pepsin output and serum pepsinogen group I were not affected by Esaprazole, while bicarbonate secretion was reduced. Antiulcer activity of Esaprazole seems to be due to the reduction of total volume of gastric secretion.
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PMID:Esaprazole effect on acid, peptic and alkaline secretion in duodenal ulcer patients. 844 49

Potential proteolytic activity of prochymosin (PCh) and pepsinogen (PG) as well as relative activity of the proteolytic fractions in the mucosal extracts of the whole stomach, pyloric region of the stomach and duodenum were investigated. The main activity in the lambs stomach after birth demonstrated PCh however a small amount of PGA activity was also present. The highest activity of PCh from the whole stomach was observed in day 2 and 3, PG activity from the whole and pyloric region of the stomach increased in the first day of life and later was not significant by changed. Mucosal extracts of the whole stomach contained 3 to 4 of pepsinogen fractions of the fast migration (Pg1, Pg2, Pg3 and Pg4) in which Pg3 was of the highest activity in the majority of lambs. Pyloric region revealed 3 fractions: Pg2, of a small and Pg3 and Pg4 of high and equal activity. In duodenum Pg3 and Pg4 were of equal activity. The beginning of Pg2, Pg3 and Pg4 relative activity changes were observed in lambs stomach in respect to increase of Pg2 and decrease of Pg3 activity. The group of 3-4 fractions of slow electrophoretic migration contained probably progastricsin of small--and prochymosin of the highest activity within this group and a small non-pepsinogen fraction.
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PMID:Prochymosin and pepsinogen potential activity and electrophoretic study of proteolytic fractions in the gastric and duodenal mucosal extracts from the first four day old lambs. 859 Sep 11

The human gastric mucosa contains five isozymogens of pepsinogen (pepsinogens PGA1-PGA5), two isozymogens of gastricsinogen (gastricsinogens PGC6-PGC7) and zymogens of cathepsins. Ratios between some individual pepsins or pepsinogens are very important from a diagnostic point of view. The ratio of pepsinogen 3 to pepsinogen 5 is significant marker of gastric cancer and gastric ulcer. High-performance ion-exchange chromatography is an easy and fast method for determination of ratios between individual proteolytic zymogens in human gastric mucosa and thus could serve for additional diagnosis of gastric diseases.
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PMID:High performance liquid chromatography enables fast determination of ratios between individual proteolytic enzymes in human gastric mucosa. 871 9


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