Pepsin

Pepsin[edit | edit source]

Pepsin is a general name for a number of proteinases (pepsin A, B, C - EC 3.4.23.1,2,3) and pepsinogens are their precursors (proenzymes). Activation of pepsinogen A to pepsin A takes place in an acidic environment, the resulting pepsin A is capable of further activation of pepsinogen via autocatalysis. 8 gastric mucosal proteases can be separated electrophoretically in agar gel: pepsinogens PG1 – PG5 form a group of immunologically identical proteins (pepsinogen I, PG-I, PGA), pepsinogens PG6 and PG7 form the group of pepsinogen II (PG-II, PGC), the last protein is cathepsin E (SMP, slow moving proteinase). Molecular weight of pepsinogen I is 42,500.

Pepsin is an endopeptidase, so it hydrolyzes peptide bonds within the molecule, breaking it down into smaller fragments. In gastric juice, it hydrolyzes bonds near amino acids that have large side chains (amino acids with aromatic residues, branched chains, and methionine).^[1]

The clinical significance[edit | edit source]

The determination of pepsin in the insulin test and the serum level of pepsinogens A and C are of clinical importance. The RIA methodology with 125 I-pepsinogen in a competitive setting is used for the determination. Pepsinogen A is a marker of mucosal atrophy and is used in genetic studies as a subclinical marker of duodenal ulcer disease. Pepsinogen C is used as a marker of gastric mucosal status (possibly the PG-A / PG-C ratio is useful) and also as a marker of infection with Helicobacter pylori as well as its eradication. There is a decreased level of pepsinogen A in patients with achlorhydria, e.g., in pernicious anemia. Recent studies have shown a significant reduction in pepsinogen-I and at the same time an increase in the level of IgA antibodies to Helicobacter pylori in gastric cancer.

Determining the ratio of the levels of both pepsinogens (PG-I : PG-II) is today considered the most advantageous serological marker related to pepsin. The ratio of PG-I to PG-II decreases significantly depending on the histological risk or the presence of vacA + positivity of Helicobacter pylori infection. The combination of determination of pepsinogen-I, gastrin-17, and antibodies to Helicobacter pylori is tested as a so-called serological biopsy, GastroPanel, in the differential diagnosis of gastritis. The risk of gastric cancer, combined with Helicobacter pylori positivity, is another area of interest in gastrointestinal tumor screening.

References[edit | edit source]

Used literature[edit | edit source]

DI MARIO, F, et al. Non-invasive tests in gastric diseases. Dig Liver Dis. 2008, vol. 40, no. 7, s. 523-30, ISSN 1590-8658 (Print), 1878-3562 (Electronic). PMID: 18439884.

CHUNG, HW, et al. Comparison of the validity of three biomarkers for gastric cancer screening: carcinoembryonic antigen, pepsinogens, and high sensitive C-reactive protein. J Clin Gastroenterol. 2009, vol. 41, no. 3, s. 19-26, ISSN 0192-0790 (Print), 1539-2031 (Electronic). PMID: 18648315.

YANAOKA, K, et al. Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Int J Cancer. 2008, vol. 123, no. 4, s. 917-26, ISSN 0020-7136 (Print), 1097-0215 (Electronic). PMID: 18508314.

XIE, XF, et al. Serum pepsinogen levels in the Japanese population: prospective study of 9 years of follow-up. Hepatogastroenterology. 2007, vol. 54, no. 78, s. 1887-90, ISSN 0172-6390 (Print). PMID: 18019741.

MIKI, K, et al. Using serum pepsinogens wisely in a clinical practice. J Dig Dis. 2007, vol. 8, no. 1, s. 8-14, ISSN 1751-2972 (Print), 1751-2980 (Electronic). PMID: 17261129.

CAO, Q, et al. Screening of atrophic gastritis and gastric cancer by serum pepsinogen, gastrin-17 and Helicobacter pylori immunoglobulin G antibodies. J Dig Dis. 2007, vol. 8, no. 1, s. 15-22, ISSN 1751-2972 (Print), 1751-2980 (Electronic). PMID: 17261130.

LOPES, AI, et al. Relationship among serum pepsinogens, serum gastrin, gastric mucosal histology and H. pylori virulence factors in a paediatric population. Scand J Gastroenterol. 2006, vol. 41, no. 5, s. 524-31, ISSN 0036-5521 (Print), 1502-7708 (Electronic). PMID: 16638693.

STEMMERMANN, GN, et al. The relation of pepsinogen group II (PGII) expression to intestinal metaplasia and gastric cancer. Histopathology. 2006, vol. 49, no. 1, s. 45-51, ISSN 0309-0167 (Print), 1365-2559 (Electronic). PMID: 16842245.

DERAKHSHAN, MH, et al. Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected with Helicobacter pylori. J Clin Pathol. 2006, vol. 59, no. 12, s. 1293-9, ISSN 0021-9746 (Print), 1472-4146 (Electronic). PMID: 16644877.

NARDONE, G, et al. Diagnostic accuracy of the serum profile of gastric mucosa in relation to histological and morphometric diagnosis of atrophy. Aliment Pharmacol Ther. 2005, vol. 22, no. 11-12, s. 1139-46, ISSN 0269-2813 (Print), 1365-2036 (Electronic). PMID: 16305728.

HOKKANEN, S, et al. Normal serum pepsinogen I levels in adults: a population-based study with special reference to Helicobacter pylori infection and parietal cell antibodies. Scand J Clin Lab Invest. 2005, vol. 65, no. 4, s. 291-9, ISSN 0036-5513 (Print), 1502-7686 (Electronic). PMID: 16076684.

GERMANÁ, B, et al. Clinical usefulness of serum pepsinogens I and II, gastrin-17 and anti-Helicobacterpylori antibodies in the management of dyspeptic patients in primary care. Dig Liver Dis. 2005, vol. 37, no. 7, s. 501-8, ISSN 1590-8658 (Print), 1878-3562 (Electronic). PMID: 15975537.

OHKUSA, T, et al. Improvement in serum pepsinogens and gastrin in long-term monitoring after eradication of Helicobacter pylori: comparison with H. pylori-negative patients. Aliment Pharmacol Ther. 2004, vol. 20, Suppl 1, s. 25-32, ISSN 0269-2813 (Print), 1365-2036 (Electronic). PMID: 15298602.

URITA, Y, et al. Serum pepsinogens as a predicator of the topography of intestinal metaplasia in patients with atrophic gastritis. Dig Dis Sci. 2004, vol. 49, no. 5, s. 795-801, ISSN 0163-2116 (Print), 1573-2568 (Electronic). PMID: 15259501.

OHATA, H, et al. Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer. 2004, vol. 109, no. 1, s. 138-43, ISSN 0020-7136 (Print), 1097-0215 (Electronic). PMID: 14735480.

KONTUREK, SJ, et al. Serum progastrin and its products, gastric acid secretion and serum pepsinogen I in gastric cancer. Digestion. 2003, vol. 68, no. 4, s. 169-77, ISSN 0012-2823 (Print), 1421-9867 (Electronic). PMID: 14671424.

VÄÄNÄNEN, H, et al. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol. 2003, vol. 15, no. 8, s. 885-91, ISSN 0954-691X (Print), 1473-5687 (Electronic). PMID: 12867799.

MIKI, K, et al. Usefulness of gastric cancer screening using the serum pepsinogen test method. Am J Gastroenterol. 2003, vol. 98, no. 4, s. 735-9, ISSN 0002-9270 (Print), 1572-0241 (Electronic). PMID: 12738449.

SANDULEANU, S, et al. Ratio between serum IL-8 and pepsinogen A/C: a marker for atrophic body gastritis. Eur J Clin Invest. 2003, vol. 33, no. 2, s. 147-54, ISSN 0014-2972 (Print), 1365-2362 (Electronic). PMID: 12588289.

BROUTET, N, et al. Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics. Br J Cancer. 2003, vol. 88, no. 8, s. 1239-47, ISSN 0007-0920 (Print), 1532-1827 (Electronic). PMID: 12698190.

SIPPONEN, P, et al. Serum levels of amidated gastrin-17 and pepsinogen I in atrophic gastritis: an observational case-control study.. Scand J Gastroenterol. 2002, vol. 37, no. 7, s. 785-91, ISSN 0036-5521 (Print), 1502-7708 (Electronic). PMID: 12190091.

MÅRDH, E, et al. Diagnosis of gastritis by means of a combination of serological analyses. Clin Chim Acta. 2002, vol. 320, no. 1-2, s. 17-27, ISSN 0009-8981 (Print), 1873-3492 (Electronic). PMID: 11983196.

LORENTE, S, et al. Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells. Gut. 2002, vol. 50, no. 1, s. 13-8, ISSN 0017-5749 (Print), 1468-3288 (Electronic). PMID: 11772960.

TABATA, H, et al. Difference in degree of mucosal atrophy between elevated and depressed types of gastric epithelial tumors. Scand J Gastroenterol. 2001, vol. 36, no. 11, s. 1134-40, ISSN 0036-5521 (Print), 1502-7708 (Electronic). PMID: 11686211.

BODGER, K, et al. Variation in serum pepsinogens with severity and topography of Helicobacter pylori-associated chronic gastritis in dyspeptic patients referred for endoscopy. Helicobacter. 2001, vol. 6, no. 3, s. 216-24, ISSN 1083-4389 (Print), 1523-5378 (Electronic). PMID: 11683924.

BERMEJO, F, et al. Basal concentrations of gastrin and pepsinogen I and II in gastric ulcer: influence of Helicobacter pylori infection and usefulness in the control of the eradication.. Gastroenterol Hepatol. 2001, vol. 24, no. 2, s. 56-62, ISSN 0210-5705. PMID: 11247290.

Sources[edit | edit source]

http://www1.lf1.cuni.cz/~kocna/glab/glency1.htm

↑ Harper's illustrated biochemistry. Thirtieth edition. New York: McGraw Hill-Education, [2015], s. 539. Lange medical book. ISBN 978-1-25-925286-0.

[1] Harper's illustrated biochemistry. Thirtieth edition. New York: McGraw Hill-Education, [2015], s. 539. Lange medical book. ISBN 978-1-25-925286-0.

[1]