The actions of carbenoxolone on enzymes and their relation to its therapeutic effect

Carbenoxolone may bind to enzymes, inhibiting or activating them. Enzymes inhibited are human pepsins 1, 3 and 5, human pepsinogens 1, 3 and 5, swine pepsin, bovine trypsin, bovine chymotrypsin, porcine elastase, human gastric proteinase 2, human gastric prostaglandin 15-OH dehydrogenase and delta-5 reductase, and pronase. Enzymes activated are papain, bovine carboxypeptidase and gastric microsomal glycosyl transferase. Enzymes unaffected are human pancreatic amylase and porcine pancreatic lipase. Binding occurs away from the active site; inhibition thus occurs when binding impedes access of substrate to, or products from, the active site, and activation when access is facilitated. Carbenoxolone causes increased secretion of mucus; this action can be explained by activation of the gastric glycosyl transferases. Carbenoxolone also causes intraluminal loss of peptic activity and diminished secretion of pepsins; these actions are explained respectively by intraluminal inhibition of the pepsins and intramucosal inactivation of the pepsinogens, particularly of the peptic ulcer-associated enzyme, pepsin 1. The healing effect of carbenoxolone in peptic ulcer involves these actions together with a reduced turnover of gastric mucosal cells. Pepsins 1 and 3 have collagenolytic activity, causing release of alpha-chains from native collagens. Pepsin 1 is five-fold the more active. Carbenoxolone inhibits peptic collagenolysis.