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Otolaryngology--head and Neck Surgery :... Sep 2017Objective Laryngopharyngeal reflux (LPR) is a common illness of otolaryngology visits. Over the past few years, pepsin has become a promising marker of LPR. The... (Review)
Review
Objective Laryngopharyngeal reflux (LPR) is a common illness of otolaryngology visits. Over the past few years, pepsin has become a promising marker of LPR. The objective of the present research is to analyze the existing literature using pepsin as a diagnostic tool of LPR through a systematic review. Data Sources PubMed (Medline), Trip Database, Cochrane Library, EMBASE, SUMsearch, and Web of Science. Review Methods The outcome assessed was the presence of pepsin in LPR patients. We included articles in which pepsin was studied in LPR patients (clinically suspected or with confirmed diagnosis). Studies with no control group, comparison group, and/or a sample size lower than 20 patients were excluded. Results Twelve studies were included. All included studies, with the exception of 2, found statistically significant differences for pepsin in cases compared with healthy controls. Conclusion Pepsin might be a reliable marker in LPR patients, although questions remain about optimal timing, location, nature, and threshold values for pepsin testing. Future investigations are necessary to clarify the best method to use pepsin in the diagnostic process of LPR.
Topics: Biomarkers; Humans; Laryngopharyngeal Reflux; Pepsin A; Reproducibility of Results; Saliva
PubMed: 28585488
DOI: 10.1177/0194599817709430 -
The Quarterly Review of Biology Jun 2002Studies on gastric digestion during 1820-1840 led to the discovery of pepsin as the agent which, in the presence of stomach acid, causes the dissolution of nutrients... (Review)
Review
Studies on gastric digestion during 1820-1840 led to the discovery of pepsin as the agent which, in the presence of stomach acid, causes the dissolution of nutrients such as meat or coagulated egg white. Soon afterward it was shown that these protein nutrients were cleaved by pepsin to diffusible products named peptones. Efforts to isolate and purify pepsin were spurred by its widespread adoption for the treatment of digestive disorders, and highly active preparations were available by the end of the nineteenth century. There was uncertainty, however, as to the chemical nature of pepsin, for some preparations exhibited the properties of proteins while other preparations failed to do so. The question was not settled until after 1930, when Northrop crystallized swine pepsin and provided convincing evidence for its identity as a protein. The availability of this purified pepsin during the 1930s also led to the discovery of the first synthetic peptide substrates for pepsin, thus providing needed evidence for the peptide structure of native proteins, a matter of debate at that time. After 1945, with the introduction of new separation methods, notably chromatography and electrophoresis, and the availability of specific proteinases, the amino acid sequences of many proteins, including pepsin and its precursor pepsinogen, were determined. Moreover, treatment of pepsin with chemical reagents indicated the participation in the catalytic mechanism of two aspartyl units widely separated in the linear sequence. Studies on the kinetics of pepsin action on long chain synthetic peptides suggested that the catalytic site was an extended structure. Similar properties were found for other "aspartyl proteinases," such as chymosin (used in cheese making), some intracellular proteinases (cathepsins), and plant proteinases. After 1975, the three-dimensional structures of pepsin and many of its relatives were determined by means of x-ray diffraction techniques, greatly extending our insight into the mechanism of the catalytic action of these enzymes. That knowledge has led to the design of new inhibitors of aspartyl proteinases, which are participants in the maturation of human immunodeficiency virus and in the generation of Alzheimer's disease.
Topics: Animals; Catalytic Domain; Crystallization; Digestion; History, 19th Century; History, 20th Century; Humans; Molecular Structure; Pepsin A
PubMed: 12089768
DOI: 10.1086/340729 -
Chest Aug 2015
Topics: Bodily Secretions; Critical Illness; Female; Gastroesophageal Reflux; Humans; Male; Pepsin A; Trachea
PubMed: 26238826
DOI: 10.1378/chest.15-0506 -
European Journal of Mass Spectrometry... Oct 2023Pepsin, because of its optimal activity at low acidic pH, has gained importance in mass spectrometric proteome research as a readily available and easy-to-handle...
Native and compactly folded conformers of pepsin are revealed and distinguished by mass spectrometric ITEM-TWO analyses of pepstatin A - pepsin complex binding strength differences.
Pepsin, because of its optimal activity at low acidic pH, has gained importance in mass spectrometric proteome research as a readily available and easy-to-handle protease. Pepsin has also been study object of protein higher-order structure analyses, but questions about how to best investigate pepsin conformers still remain. We first determined dependencies of pepsin ion charge structures on solvent pH which indicated the existence of (a) natively folded pepsin (N) which by nanoESI-MS analysis gave rise to a narrow charge state distribution with an 11-fold protonated most intense ion signal, (b) unfolded pepsin (U) with a rather broad ion charge state distribution whose highest ion signal carried 25 protons, and (c) a compactly folded pepsin conformer (C) with a narrow charge structure and a 12-fold protonated ion signal in the center of its charge state envelope. Because pepsin is a protease, unfolded pepsin became its own substrate in solution at pH 6.6 since at this pH some portion of pepsin maintained a compact/native fold which displayed enzymatic activity. Subsequent mass spectrometric ITEM-TWO analyses of pepstatin A - pepsin complex dissociation reactions in the gas phase confirmed a very strong binding of pepstatin A by natively folded pepsin (N). ITEM-TWO further revealed the existence of two compactly folded pepsin conformers (C and C) which also were able to bind pepstatin A. Binding strengths of the respective compactly folded pepsin conformer-containing complexes could be determined and apparent gas phase complex dissociation constants and reaction enthalpies differentiated these from each other and from the pepstatin A - pepsin complex which had been formed from natively folded pepsin. Thus, ITEM-TWO turned out to be well suited to pinpoint pepsin conformers by interrogating quantitative traits of pepstatin A - pepsin complexes in the gas phase.
Topics: Pepsin A; Pepstatins; Spectrometry, Mass, Electrospray Ionization
PubMed: 37259551
DOI: 10.1177/14690667231178999 -
International Journal of Biological... Dec 2020Pepsin, as the main protease of the stomach, plays an important role in the digestion of food proteins into smaller peptides and performs about 20% of the digestive...
Pepsin, as the main protease of the stomach, plays an important role in the digestion of food proteins into smaller peptides and performs about 20% of the digestive function. The role of pepsin in the development of gastrointestinal ulcers has also been studied for many years. Edible drugs that enter the body through the gastrointestinal tract will interact with this enzyme as one of the first targets. Continuous and long-term usage of some drugs will cause chronic contact of the drug with this protein, and as a result, the structure and function of pepsin may be affected. Therefore, the possible effect of atenolol and diltiazem on the structure and activity of pepsin was studied. The interaction of drugs with pepsin was evaluated using various experimental methods including UV-Visible spectroscopy, fluorescence spectroscopy, FTIR and enzymatic activity along with computational approaches. It was showed that after binding of atenolol and diltiazem to pepsin, the inherent fluorescence of the protein is quenched. Determination of the thermodynamic parameters of interactions between atenolol and diltiazem with pepsin indicates that the major forces in the formation of the protein-drug complexes are hydrophobic forces and also atenolol has a stronger protein bonding than diltiazem. Additional tests also show that the protease activity of pepsin, decreases and increases in the presence of atenolol and diltiazem, respectively. Investigation of the FTIR spectrum of the protein in the presence and absence of atenolol and diltiazem show that in the presence of atenolol the structure of protein has slightly changed. Molecular modeling studies, in agreement with the experimental results, confirm the binding of atenolol and diltiazem to the enzyme pepsin and show that the drugs are bind close to the active site of the enzyme. Finally, from experimental and computational results, it can be concluded that atenolol and diltiazem interact with the pepsin and change its structure and protease activity.
Topics: Atenolol; Binding Sites; Catalytic Domain; Diltiazem; Humans; Hydrogen Bonding; Molecular Docking Simulation; Pepsin A; Peptide Hydrolases; Protein Binding; Spectrometry, Fluorescence; Structure-Activity Relationship
PubMed: 33096169
DOI: 10.1016/j.ijbiomac.2020.10.118 -
The Medical Clinics of North America Nov 1974
Review
Topics: Acetylcholine; Adrenal Cortex; Animals; Antacids; Anticoagulants; Carrageenan; Cholecystokinin; Duodenal Ulcer; Enzyme Activation; Gastric Acidity Determination; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Pepsin A; Pepsinogens; Peptic Ulcer; Secretin; Vagotomy; Vagus Nerve; Xanthines
PubMed: 4610293
DOI: 10.1016/s0025-7125(16)32070-3 -
The Journal of General Physiology Mar 1962Evidence relating to the structure and properties of swine pepsinogen and pepsin has been reviewed and used to suggest a tentative two dimensional picture of the...
Evidence relating to the structure and properties of swine pepsinogen and pepsin has been reviewed and used to suggest a tentative two dimensional picture of the skeleton of these two proteins. When pepsinogen, a folded single peptide chain, is converted to pepsin, there is a profound change in the physical and chemical properties of the protein. In an as yet unknown manner, except that it is initiated by a peptic cleavage of the protein chain, a single enzymic site is formed. This site is made up, quite probably, of the secondary carboxyl group of glutamic acid or of aspartic acid and a tyrosine phenol group in close proximity so that they can form hydrogen or hydrophobic bonds with the substrate in some unique manner that permits hydrolysis to occur at an accelerated rate.
Topics: Animals; Hydrogen-Ion Concentration; Hydrolysis; Pepsin A; Pepsinogen A; Pepsinogens; Swine; Tyrosine
PubMed: 13906833
DOI: No ID Found -
Carbohydrate Polymers Feb 2014Pepsin (porcine stomach mucosa, E.C. 3.4.23.1), an acid protease catalyzes the hydrolysis (debranching) of guar galactomannan (GG), a co-polymer of mannose and galactose...
BACKGROUND
Pepsin (porcine stomach mucosa, E.C. 3.4.23.1), an acid protease catalyzes the hydrolysis (debranching) of guar galactomannan (GG), a co-polymer of mannose and galactose residues thereby showing its non-specific catalysis towards glycosidic substrates.
RESULTS AND CONCLUSIONS
Use of non-specific inhibitors, chemical modification agents and peptide mapping of native and GG--bound pepsin upon proteolytic digestion with Staphylococcus aureus V8 protease revealed the involvement of Asp(138) residue in the catalysis, which was confirmed by computational modelling studies.
GENERAL SIGNIFICANCE
Here we show a novel mode of catalysis (other than proteolysis) by porcine pepsin with a different active site residue.
Topics: Amino Acid Sequence; Animals; Catalysis; Chromatography, Gel; Chromatography, High Pressure Liquid; Crystallography, X-Ray; Cyamopsis; Galactose; Mannans; Molecular Docking Simulation; Molecular Sequence Data; Native Polyacrylamide Gel Electrophoresis; Pepsin A; Peptide Mapping; Sequence Homology, Amino Acid; Swine
PubMed: 24507326
DOI: 10.1016/j.carbpol.2013.11.043 -
BMC Gastroenterology Nov 2017Functional dyspepsia (FD) is a gastrointestinal disorder characterized by recurrent and diverse symptoms and pathophysiology that remains unexplained following routine... (Observational Study)
Observational Study
BACKGROUND
Functional dyspepsia (FD) is a gastrointestinal disorder characterized by recurrent and diverse symptoms and pathophysiology that remains unexplained following routine clinical investigation. Enzynorm®f is a pharmaceutical preparation comprising fixed amounts of pepsin of biological origin and organically bound acid in the form of amino acid hydrochloride. It is traditionally used as a mild agent to support gastric function and to stimulate the stomach's proteolytic activities in FD.
METHODS
In a non-interventional, observational, post-marketing surveillance study, patients with an established diagnosis of FD were treated with a fixed combination of pepsin and amino acid hydrochloride taken as tablets three times daily for 6 weeks. The primary objective of this study was to assess the change in symptoms using the validated Gastrointestinal Symptom Score (GIS©). Secondary objectives included patients' assessment of their gastrointestinal symptoms as well as treatment safety and tolerability.
RESULTS
A total of 97 patients (mean age 58.4 ± 13.9 years; 63.2% females) were included in the study, with 72 data having GIS© score data at baseline and at 6 weeks, and 34 also at 3 weeks. The overall GIS© sum score decreased by 4.1 (p < 0.0001) from 11.6 (±4.8) at baseline to 7.4 (± 4.6) reflecting an improvement of clinical symptomatology after 6 weeks of treatment. In a subgroup of 70 patients who had FD meeting the Rome III criteria a GIS© score reduction of ≥50% was observed after 3 weeks treatment in 24% and in 30.8% after 6 weeks. Adverse events were mostly gastrointestinal in nature and consistent with the underlying disease; no unexpected adverse reactions were reported. Twenty-seven patients discontinued the study, mostly because of gastrointestinal symptoms.
CONCLUSION
The results of this study support the efficacy of a fixed combination of pepsin and amino acid hydrochloride for the treatment of patients with FD and also suggest good to moderate treatment tolerability. These findings should be further explored in a randomised, placebo-controlled clinical trial.
CLINICAL TRIAL REGISTRATION
This study has been retrospectively registered in the ClinicalTrials.gov registry, trial identifier NCT03076411 .
Topics: Amino Acids; Drug Administration Schedule; Drug Combinations; Dyspepsia; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Patient Outcome Assessment; Pepsin A; Product Surveillance, Postmarketing; Treatment Outcome
PubMed: 29178842
DOI: 10.1186/s12876-017-0675-9 -
Forensic Science International Jan 1992Reported is a simple and reliable method for identifying the presence of gastric fluid in forensic samples by an assay that reveals the pepsin activity. These samples...
Reported is a simple and reliable method for identifying the presence of gastric fluid in forensic samples by an assay that reveals the pepsin activity. These samples are usually vomit found at the scene of a crime, either in fresh form or as a dried stain on clothing. The pepsin within the sample is assayed for its proteolytic activity which is revealed in a fibrin blue-agarose gel plate, as a result of an enzymatic reactivity that takes the form of a concentric, blue, translucent ring around the tested sample. Apart from being able to determine the pepsin content of fresh or recent forensic samples, this method has also achieved positive reactions in aged gastric fluid stains that were kept at room temperature. No body fluids other than the gastric fluid and no proteolytic enzymes other than pepsin show a positive reaction with the use of this method. This method has an additional advantage, in that the enzymatic activity seen on the gel plate can be photographed and the gel plate, on drying, can also be preserved as evidence.
Topics: Animals; Chymotrypsin; Gastric Juice; Gastrointestinal Contents; Humans; Immunodiffusion; Milk, Human; Nasal Mucosa; Papain; Pepsin A; Saliva; Semen; Swine; Trypsin; Vomiting
PubMed: 1601352
DOI: 10.1016/0379-0738(92)90110-i