Review article: human pepsins - their multiplicity, function and role in reflux disease.
Human gastric juice contains a multiplicity of proteinases. These are classified as aspartic proteinases because of enzymic activity dependent on two oppositely placed aspartic acids in the active site region. At least seven zones of activity can be visualized by agar gel electrophoresis and a similar number of separate proteins resolved by high performance ion exchange chromatography. The major enzyme secreted (up to 70% of the total) pepsin 3b is sensitive to the selective inhibitor pepstatin whereas gastricsin or pepsin 5 (20% of the total) is not. Minor enzymes including pepsin 1, which has an associated proteincarbohydrate complex attached is variable and can be < 5% in normal and up to 20% of the total as in peptic ulcer patients. The activity of these enzymes depends on the substrate and pH with significant digestion occurring up to pH 4.5. It has also been shown that these enzymes can bind to substrates like collagen up to pH 5.5. In gastric secretion studies of patients with reflux oesophagitis the amount of pepsin and the profile of the enzymes in basal secretions, and that after pentagastrin stimulation, was found to be not different from healthy non-refluxers. Thus the problem with reflux is that gastric juice appears in the oesophagus, an area without any natural protection from proteolytic damage. The ability to reduce gastric secretion is therefore important in effective treatment. However, being able also to inhibit enzymic activity or protect substrates from damage using alginates offers considerable scope for future therapies.
Roberts
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NB
Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospital, Liverpool, UK. n.b.roberts@liverpool.ac.uk
D004942:Esophagitis, Peptic / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism; D005764:Gastroesophageal Reflux / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010418:Pentagastrin / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism*; D010436:Pepstatins / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D009626:Terminology as Topic
D010436:Pepstatins; D011480:Protease Inhibitors; D010434:Pepsin A; C020557:gastricsin; D010418:Pentagastrin; C031375:pepstatin