title: Alginate as a protease inhibitor in vitro and in a model gut system; selective inhibition of pepsin but not trypsin.
abstract: Alginates are widely used in the food and medical industries, including as a Gastro-Oesophagul Reflux treatment. This work investigates the inhibitory effects of alginate on the reflux aggressors trypsin and pepsin and the role of alginate-substrate binding, pH and alginate structure on inhibition. Alginates were shown to reduce pepsin activity by up to 53.9% (±9.5SD) in vitro. Strong positive correlation between alginate mannuronate residue frequency and levels of pepsin inhibition was observed. Limited inhibition of trypsin was shown. Viscometric observations of pH dependent interactions between alginate and protein suggest a mechanism whereby pH dependent ionic interactions reduce substrate availability to enzyme at acidic pH. To understand how dietary protein digestion is affected by alginate, proteolytic digestion was investigated in an in vitro model of the upper digestive tract. Significant inhibition of proteolysis was shown in the gastric phase of digestion, but not the small intestinal phase.
authors.affiliation: Institute for Cell and Molecular Biosciences (ICaMB), Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. Electronic address: peter.chater@ncl.ac.uk.
authors.forename: Peter Ian
authors.initials: PI
authors.lastname: Chater
authors.affiliation: Institute for Cell and Molecular Biosciences (ICaMB), Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Wilcox
authors.affiliation: Nanyang Polytechnic, Food and Human Nutrition Department, Newcastle University Office, 180 Ang Mo Kio, Avenue 8, 569830 Singapore, Singapore.
authors.forename: Iain A
authors.initials: IA
authors.lastname: Brownlee
authors.affiliation: Institute for Cell and Molecular Biosciences (ICaMB), Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Pearson
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000201:enzymology*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D010179:Pancreas / Q000378:metabolism; D010434:Pepsin A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism*; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology; D014783:Viscosity
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D011480:Protease Inhibitors; D012710:Serum Albumin, Bovine; D020723:Glucuronic Acid; D014360:Trypsin Inhibitor, Kunitz Soybean; D014357:Trypsin; D010434:Pepsin A
keywords: Alginate; Model gut system; Pepsin; Proteolysis; Trypsin