pepsin a


Summary: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice.

Top Publications

  1. Kopper R, Odum N, Sen M, Helm R, Steve Stanley J, Wesley Burks A. Peanut protein allergens: gastric digestion is carried out exclusively by pepsin. J Allergy Clin Immunol. 2004;114:614-8 pubmed
    ..One estimate of the allergenic potential of a possible protein allergen is its stability under simulated gastric conditions...
  2. Mittag D, Akkerdaas J, Ballmer Weber B, Vogel L, Wensing M, Becker W, et al. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol. 2004;114:1410-7 pubmed
    ..We recently described patients with soybean allergy mainly mediated by cross-reactivity to birch pollen allergens. A majority of those patients were reported to have peanut allergy...
  3. Zavros Y, Waghray M, Tessier A, Bai L, Todisco A, L Gumucio D, et al. Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation. J Biol Chem. 2007;282:33265-74 pubmed
    ..This cleavage was blocked by the proton pump inhibitor omeprazole and mediated by the acid-activated protease pepsin A. Pepsin A was also the protease responsible for processing Shh in tissue extracts from human stomach...
  4. Kim T, Lee K, Yeo M, Kim D, Cho S. Pepsin detection in the sputum/saliva for the diagnosis of gastroesophageal reflux disease in patients with clinically suspected atypical gastroesophageal reflux disease symptoms. Digestion. 2008;77:201-6 pubmed publisher
    ..Pepsin measurement in the sputum/saliva collected at the time of symptoms provides a sensitive, non-invasive method for diagnosing GERD in patients with clinically suspected atypical GERD symptoms. ..
  5. Ervine E, McMaster C, McCallion W, Shields M. Pepsin measured in induced sputum--a test for pulmonary aspiration in children?. J Pediatr Surg. 2009;44:1938-41 pubmed publisher
    ..The analysis of pepsin in sputum obtained by sputum induction is therefore not useful in the investigation of reflux-related respiratory disease. ..
  6. Cox C, Secor S. Integrated postprandial responses of the diamondback water snake, Nerodia rhombifer. Physiol Biochem Zool. 2010;83:618-31 pubmed publisher
    ..rhombifer is generally modest and matched in magnitude. ..
  7. Koppelman S, Hefle S, Taylor S, de Jong G. Digestion of peanut allergens Ara h 1, Ara h 2, Ara h 3, and Ara h 6: a comparative in vitro study and partial characterization of digestion-resistant peptides. Mol Nutr Food Res. 2010;54:1711-21 pubmed publisher
    ..Trypsin digestion of Ara h 2 similarly resulted in large residual peptides and these were identified. Ara h 2 and Ara h 6 are considerably more stable towards digestion than Ara h 1 and Ara h 3. ..
  8. Zhang H, Kazazic S, Schaub T, Tipton J, Emmett M, Marshall A. Enhanced digestion efficiency, peptide ionization efficiency, and sequence resolution for protein hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem. 2008;80:9034-41 pubmed
    ..Such assignments of highly overlapped fragments promise to greatly enhance the accuracy and sequence resolution for determining conformational differences resulting from ligand binding or protein-protein interactions. ..
  9. Clement F, Venkatesh Y. Dietary garlic (Allium sativum) lectins, ASA I and ASA II, are highly stable and immunogenic. Int Immunopharmacol. 2010;10:1161-9 pubmed publisher

More Information


  1. Kubota K, Metoki Y, Athauda S, Shibata C, Takahashi K. Stability profiles of nepenthesin in urea and guanidine hydrochloride: comparison with porcine pepsin A. Biosci Biotechnol Biochem. 2010;74:2323-6 pubmed aspartic endopeptidase from the pitcher fluid of Nepenthes, was found to be markedly less stable than porcine pepsin A when treated with urea or guanidine hydrochloride...
  2. Farrell S, McMaster C, Gibson D, Shields M, McCallion W. Pepsin in bronchoalveolar lavage fluid: a specific and sensitive method of diagnosing gastro-oesophageal reflux-related pulmonary aspiration. J Pediatr Surg. 2006;41:289-93 pubmed
    ..This study suggests that GOR-related aspiration plays a role in chronic cough in children with known GOR. Detecting pepsin in BAL fluid may therefore become an important adjunct in patient selection for antireflux surgery. ..
  3. Fu T, Abbott U, Hatzos C. Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid-a comparative study. J Agric Food Chem. 2002;50:7154-60 pubmed
    ..Food allergens were not necessarily more resistant to digestion than nonallergenic proteins. There was not a clear relationship between digestibility measured in vitro and protein allergenicity. ..
  4. Blondeau K, Mertens V, Vanaudenaerde B, Verleden G, Van Raemdonck D, Sifrim D, et al. Gastro-oesophageal reflux and gastric aspiration in lung transplant patients with or without chronic rejection. Eur Respir J. 2008;31:707-13 pubmed
    ..Pepsin was a more general marker and bile acids a more specific marker that might be associated with bronchiolitis obliterans syndrome. Proton pump inhibitor treatment did not prevent nonacid reflux and gastric aspiration. ..
  5. Knight J, Lively M, Johnston N, Dettmar P, Koufman J. Sensitive pepsin immunoassay for detection of laryngopharyngeal reflux. Laryngoscope. 2005;115:1473-8 pubmed
    ..Detection of pepsin in throat sputum by immunoassay appears to provide a sensitive, noninvasive method to detect LPR. ..
  6. Ufberg J, Bushra J, Karras D, Satz W, Kueppers F. Aspiration of gastric contents: association with prehospital intubation. Am J Emerg Med. 2005;23:379-82 pubmed
    ..008; odds ratio, 3.5; 95% CI, 1.34-9.08). Patients endotracheally intubated in the PH setting are more likely to have aspirated gastric contents than those intubated in the ED. ..
  7. Hughes A, Green J, Piontkivska H, Roberts R. Aspartic proteinase phylogeny and the origin of pregnancy-associated glycoproteins. Mol Biol Evol. 2003;20:1940-5 pubmed
    ..two groups in turn form a sister group to a group of digestive enzymes from birds and mammals, which includes pepsin A. Sequence similarity in the promoter region of artiodactyl PAGs and mouse pepsin F also supported a close ..
  8. Roberts N, Taylor W. Comparative pepstatin inhibition studies on individual human pepsins and pepsinogens 1,3 and 5(gastricsin) and pig pepsin A. J Enzyme Inhib Med Chem. 2003;18:209-17 pubmed
    ..The explanation for the reduced affinity of pepstatin to pepsin 5(gastricsin) needs further study by co-crystallisation X-ray analysis. ..
  9. Vallejo F, Gil Izquierdo A, Pérez Vicente A, García Viguera C. In vitro gastrointestinal digestion study of broccoli inflorescence phenolic compounds, glucosinolates, and vitamin C. J Agric Food Chem. 2004;52:135-8 pubmed
    ..Thus, glucosinolates were mainly degraded by gastric conditions, whereas phenolic compounds and vitamin C were degraded by intestinal conditions. ..
  10. Carginale V, Trinchella F, Capasso C, Scudiero R, Riggio M, Parisi E. Adaptive evolution and functional divergence of pepsin gene family. Gene. 2004;333:81-90 pubmed
    ..The results of functional divergence analysis provided statistical evidence for shifted evolutionary rate after gene duplication. ..
  11. Adhami T, Goldblum J, Richter J, Vaezi M. The role of gastric and duodenal agents in laryngeal injury: an experimental canine model. Am J Gastroenterol. 2004;99:2098-106 pubmed
    ..ii) Duodenal agents do not play a significant role in causing laryngeal injury. (iii) Aggressive acid suppression should eliminate the injurious potential of any gastroduodenal refluxate. ..
  12. Ufberg J, Bushra J, Patel D, Wong E, Karras D, Kueppers F. A new pepsin assay to detect pulmonary aspiration of gastric contents among newly intubated patients. Am J Emerg Med. 2004;22:612-4 pubmed
    ..Pepstatin halted pepsin activity in all positive samples, ensuring that positive results were due to pepsin. A pepsin-specific assay is extremely reliable for detecting gastric contents in humans. ..
  13. Potluri S, Friedenberg F, Parkman H, Chang A, MacNeal R, Manus C, et al. Comparison of a salivary/sputum pepsin assay with 24-hour esophageal pH monitoring for detection of gastric reflux into the proximal esophagus, oropharynx, and lung. Dig Dis Sci. 2003;48:1813-7 pubmed
    ..In conclusion, detection of pepsin in the saliva and/or sputum may provide a noninvasive method to test for the proximal reflux of gastric contents. ..
  14. Thomas K, Aalbers M, Bannon G, Bartels M, Dearman R, Esdaile D, et al. A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins. Regul Toxicol Pharmacol. 2004;39:87-98 pubmed
    ..0 (77%). Conclusions. These data demonstrate that this common protocol for evaluating the in vitro digestibility of proteins is reproducible and yields consistent results when performed using the same proteins at different laboratories. ..
  15. Tack J. Review article: the role of bile and pepsin in the pathophysiology and treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006;24 Suppl 2:10-6 pubmed
    ..The therapeutic options for the non-acid component of the refluxate, including acid suppression, prokinetics, baclofen, surgery and mucosal protective agents like alginates, are discussed. ..
  16. Schreiber S, Bücker R, Groll C, Azevedo Vethacke M, Scheid P, Gatermann S, et al. Gastric antibacterial efficiency is different for pepsin A and C. Arch Microbiol. 2006;184:335-40 pubmed
    ..We found that pepsin C completely inactivates H. pylori at proteolytic activities of 2 (pH 5) and 20 (pH 2) U/ml. In contrast, the activities of pepsin A and chymosin required to affect Helicobacter motility were ten times higher.
  17. Kalantzi L, Goumas K, Kalioras V, Abrahamsson B, Dressman J, Reppas C. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm Res. 2006;23:165-76 pubmed
  18. Schreiber S, Bücker R, Groll C, Azevedo Vethacke M, Garten D, Scheid P, et al. Rapid loss of motility of Helicobacter pylori in the gastric lumen in vivo. Infect Immun. 2005;73:1584-9 pubmed
    ..pylori in the gastric chymus to only a few minutes by rapidly inhibiting active motility. It is therefore likely that this short period of resistance in the gastric lumen is one of the most critical phases of Helicobacter infection. ..
  19. Adje E, Balti R, Kouach M, Dhulster P, Guillochon D, Nedjar Arroume N. Obtaining antimicrobial peptides by controlled peptic hydrolysis of bovine hemoglobin. Int J Biol Macromol. 2011;49:143-53 pubmed publisher
    ..1 to 1 ?M. Among these peptides, 13 new antibacterial peptides are obtained only in these new hydrolysis conditions. ..
  20. Mudgal P, Daubert C, Clare D, Foegeding E. Effect of disulfide interactions and hydrolysis on the thermal aggregation of ?-lactoglobulin. J Agric Food Chem. 2011;59:1491-7 pubmed publisher
    ..35, beyond the existence of limited disulfide interactions, acid hydrolysis and noncovalent interactions more likely play a crucial role in defining the functionality of acidified powdered modified whey ingredients. ..
  21. Yao X, Bunt C, Cornish J, Quek S, Wen J. Improved RP-HPLC method for determination of bovine lactoferrin and its proteolytic degradation in simulated gastrointestinal fluids. Biomed Chromatogr. 2013;27:197-202 pubmed publisher
    ..The proteolytic study indicated that this validated RP-HPLC was able to evaluate bLf stability though monitoring the derivatization products. ..
  22. Zhao Q, Liu H, Zhang Y, Zhang Y. Engineering of protease-resistant phytase from Penicillium sp.: high thermal stability, low optimal temperature and pH. J Biosci Bioeng. 2010;110:638-45 pubmed publisher
    ..0 by facilitating the interaction between the substrate and the catalytic centre. The substitution of N354D influenced the pH profile by weakening the bondage with the side chain of D353, which caused a pKa shift of the catalytic centre. ..
  23. Dekkers B, Kolodziejczyk E, Acquistapace S, Engmann J, Wooster T. Impact of gastric pH profiles on the proteolytic digestion of mixed βlg-Xanthan biopolymer gels. Food Funct. 2016;7:58-68 pubmed publisher
  24. Wang R, Xie Y, Zhang Y, Kang X, Wang X, Ge B, et al. Comparative study of the binding of pepsin to four alkaloids by spectrofluorimetry. Spectrochim Acta A Mol Biomol Spectrosc. 2013;108:62-74 pubmed publisher
    ..Results showed that aminophylline was the stronger quencher and bound to pepsin with higher affinity than other three alkaloids. ..
  25. Rajamohamed S, Aryee A, Hucl P, Patterson C, Boye J. In vitro gastrointestinal digestion of glabrous canaryseed proteins as affected by variety and thermal treatment. Plant Foods Hum Nutr. 2013;68:306-12 pubmed publisher
    ..Furthermore, roasting appeared to have a greater impact on in vitro protein digestibility than boiling. ..
  26. Al Abdulla I, Casewell N, Landon J. Single-reagent one-step procedures for the purification of ovine IgG, F(ab')2 and Fab antivenoms by caprylic acid. J Immunol Methods. 2014;402:15-22 pubmed publisher
  27. Imelio N, Marini A, Spelzini D, Picó G, Farruggia B. Pepsin extraction from bovine stomach using aqueous two-phase systems: molecular mechanism and influence of homogenate mass and phase volume ratio. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;873:133-8 pubmed publisher
    ..The best purification factors were obtained with PEG600/potassium phosphate with low top-bottom volume ratio using 15% of bovine stomach homogenate in the system total mass. ..
  28. Margatan W, Ruud K, Wang Q, Markowski T, Ismail B. Angiotensin converting enzyme inhibitory activity of soy protein subjected to selective hydrolysis and thermal processing. J Agric Food Chem. 2013;61:3460-7 pubmed publisher
    ..This work demonstrated, for the first time, that selective hydrolysis to release peptides with ACE inhibitory activity can be accomplished without inducing extensive hydrolysis and performing unnecessary fractionation. ..
  29. Argyri K, Tako E, Miller D, Glahn R, Komaitis M, Kapsokefalou M. Milk peptides increase iron dialyzability in water but do not affect DMT-1 expression in Caco-2 cells. J Agric Food Chem. 2009;57:1538-43 pubmed publisher
    ..However, dialyzability from milk was enhanced by the addition of a more concentrated lyophilized peptide fraction. ..
  30. Sams L, Paume J, Giallo J, Carrière F. Relevant pH and lipase for in vitro models of gastric digestion. Food Funct. 2016;7:30-45 pubmed publisher
    ..Most of these properties have been known for more than two decades and should provide a rational basis for the replacement of gastric lipase by other lipases when gastric lipase is not available. ..
  31. Kulis M, MacQueen I, Li Y, Guo R, Zhong X, Burks A. Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy. J Allergy Clin Immunol. 2012;130:716-23 pubmed publisher
    ..Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy. ..
  32. Madureira A, Campos D, Oliveira A, Sarmento B, Pintado M, Gomes A. Insights into the protective role of solid lipid nanoparticles on rosmarinic acid bioactivity during exposure to simulated gastrointestinal conditions. Colloids Surf B Biointerfaces. 2016;139:277-84 pubmed publisher
    ..A controlled release of RA from SLN was achieved and a significant absorption was observed at intestinal cells. Overall, SLN produced with witepsol showed a higher stability than carnauba SLN. ..
  33. Rosen R, Johnston N, Hart K, Khatwa U, Nurko S. The presence of pepsin in the lung and its relationship to pathologic gastro-esophageal reflux. Neurogastroenterol Motil. 2012;24:129-33, e84-5 pubmed publisher
    ..001). Lung pepsin cannot predict pathologic reflux in the esophagus, but its correlation with lung inflammation suggests that pepsin may be an important biomarker for reflux-related lung disease. ..
  34. Stewart R, Coad J, Reynolds G, Pedley K. New Zealand green-lipped mussels (Perna canaliculus) enhance non-haem iron absorption in vitro. Br J Nutr. 2012;108:949-52 pubmed publisher
    ..Beef and GLM digestates both significantly enhanced Fe absorption compared with egg albumin. In conclusion, GLM digestate significantly enhances non-haem Fe uptake in Caco-2 cells with a similar magnitude to that of beef. ..
  35. Block B, Kuo E, Zalzal H, Escobar H, Rose M, Preciado D. In vitro effects of acid and pepsin on mouse middle ear epithelial cell viability and MUC5B gene expression. Arch Otolaryngol Head Neck Surg. 2010;136:37-42 pubmed publisher
  36. Shanmugam G, Selvi C, Mandal A. Ethanol and acetonitrile induces conformational changes in porcine pepsin at alkaline denatured state. Int J Biol Macromol. 2012;51:590-6 pubmed publisher
    ..The current results have important implications in understanding the effect of co-solvents on the conformation of proteins in the "denatured state". ..
  37. Misra A, Kumar S, Verma A, Chanana N, Das M, Dhawan V, et al. Safety evaluation of genetically modified mustard (V4) seeds in terms of allergenicity: comparison with native crop. GM Crops Food. 2012;3:273-82 pubmed publisher
    ..Collectively, our data demonstrate substantially equivalent allergic responses against GM as well as its native counterpart. Therefore, the GM mustard may be as safe as its native counterpart with reference to allergenic responses. ..
  38. Robitaille G, Lapointe C, Leclerc D, Britten M. Effect of pepsin-treated bovine and goat caseinomacropeptide on Escherichia coli and Lactobacillus rhamnosus in acidic conditions. J Dairy Sci. 2012;95:1-8 pubmed publisher
    ..coli in acidic media, but improved the resistance of L. rhamnosus to acid stress. The peptide fragment accountable for bactericidal activity is the N-terminal region ?-casein f(106-124). ..
  39. Karava N, Mahoney R. Lyophilization decreases the formation of dialyzable iron by extraction and digestion of chicken breast muscle. Int J Food Sci Nutr. 2011;62:397-403 pubmed publisher
    ..Reduced formation of dialyzable iron by both mechanisms following lyophilization could be explained by sulfhydryl oxidation and impaired digestion due to protein crosslinking. ..
  40. Jaremko L, Jaremko M, Pasikowski P, Cebrat M, Stefanowicz P, Lisowski M, et al. The immunosuppressive activity and solution structures of ubiquitin fragments. Biopolymers. 2009;91:423-31 pubmed publisher
    ..Although the peptide exhibited a well-defined conformation in methanol, its structure was distinct from the corresponding 50-59 fragment in the native ubiquitin molecule. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 423-431, 2009. ..
  41. Spelzini D, Peleteiro J, Picó G, Farruggia B. Polyethyleneglycol-pepsin interaction and its relationship with protein partitioning in aqueous two-phase systems. Colloids Surf B Biointerfaces. 2008;67:151-6 pubmed publisher
    ..Polyethyleneglycol of average molecular mass 8000 showed a cooperative interaction between the polymer and protein molecules which was independent of the PEG concentration. ..
  42. Ritala A, Wahlström E, Holkeri H, Hafren A, Mäkeläinen K, Baez J, et al. Production of a recombinant industrial protein using barley cell cultures. Protein Expr Purif. 2008;59:274-81 pubmed publisher
  43. Tay W, Bryant J, Martin P, Nix A, Cusack B, Rosenberry T. A mass spectrometric approach for characterization of amyloid-? aggregates and identification of their post-translational modifications. Biochemistry. 2012;51:3759-66 pubmed publisher
    ..Therefore, this methodology shows great promise for structural analysis and identification of post-translational modification(s) in endogenous A? oligomers. ..
  44. Erickson Levendoski E, Sivasankar M. Role for ion transport in porcine vocal fold epithelial defense to acid challenge. Otolaryngol Head Neck Surg. 2012;146:272-8 pubmed publisher
    ..These findings contribute to the identification of the mechanisms underlying vocal fold defense to reflux and offer implications for the development of treatments for reflux-induced vocal fold injury. ..
  45. Haddar A, Sellimi S, Ghannouchi R, Alvarez O, Nasri M, Bougatef A. Functional, antioxidant and film-forming properties of tuna-skin gelatin with a brown algae extract. Int J Biol Macromol. 2012;51:477-83 pubmed publisher
    ..Extracts of brown algae could be useful additives to obtain edible films from tuna-skin gelatin with interesting functional and antioxidant properties. ..
  46. Cao M, Chen W, Du C, Yoshida A, Lan W, Liu G, et al. Pepsinogens and pepsins from Japanese seabass (Lateolabrax japonicus). Comp Biochem Physiol B Biochem Mol Biol. 2011;158:259-65 pubmed publisher
    ..The effective digestion of fish and shrimp muscular proteins by pepsins indicated their physiological function in the degradation of food proteins. ..
  47. Woodland P, Sifrim D. The refluxate: The impact of its magnitude, composition and distribution. Best Pract Res Clin Gastroenterol. 2010;24:861-71 pubmed publisher
    ..The manifestation of disease, however, is not entirely reliant on the refluxate, which must be considered in the context of the genetic, environmental and psychological susceptibility of the individual. ..
  48. Sams V, Lawson C, Humphrey C, Brantley S, Schumacher L, Karlstad M, et al. Effect of rotational therapy on aspiration risk of enteral feeds. Nutr Clin Pract. 2012;27:808-11 pubmed publisher
    ..552). The results of this study indicate that enteral nutrition should not be delayed or stopped to position the tube in patients with ARDS on rotational therapy. ..
  49. Rechtman M, Har Noy O, Bar Yishay I, Fishman S, Adamovich Y, Shaul Y, et al. Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1alpha. FEBS Lett. 2010;584:2485-90 pubmed publisher
    ..We suggest curcumin as a host targeted therapy for HBV infection that may complement current virus-specific therapies. ..
  50. Yang H, Gurgel P, Williams D, Bobay B, Cavanagh J, Muddiman D, et al. Binding site on human immunoglobulin G for the affinity ligand HWRGWV. J Mol Recognit. 2010;23:271-82 pubmed publisher
    ..The results support the fact that a peptide as small as a hexamer can have specific interactions with large proteins such as hIgG. ..
  51. Rawlings N, Bateman A. Pepsin homologues in bacteria. BMC Genomics. 2009;10:437 pubmed publisher
    ..The homologues from oceanic bacteria are most closely related to memapsins (or BACE-1 and BACE-2), but are so divergent that they are close to the root of the phylogenetic tree and to the division of the A1 family into two subfamilies. ..
  52. Samuels T, Handler E, Syring M, Pajewski N, Blumin J, Kerschner J, et al. Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux. Ann Otol Rhinol Laryngol. 2008;117:688-95 pubmed
    ..These mucin genes were up-regulated after exposure to low pH in vitro (p < 0.005). Pepsin inhibited this up-regulation (p <0.001). Reflux laryngitis is associated with down-regulation of mucin gene expression. ..
  53. Tan J, Wang L, Huang Z, Li Y, Tian W, Liu X, et al. [The expression and significance of pepsin in laryngeal carcinoma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51:593-9 pubmed publisher
    ..Pepsin expression in laryngeal tissue increases in patients with vocal cord leukoplakia and laryngeal carcinoma, contributing to the development of laryngopharyngeal carcinogenesis. ..