Electrophoretic and Immunochemical Demonstration of the Existence of Four Human Pepsinogens*

Abstract

Previous work from this laboratory has shown 4 electrophoretically distinct constituents of human gastric mucosal extracts displaying proteolytic activity at pH 2. This study was undertaken to define the nature of these components. Activation of porcine pepsinogen to pepsin at pH 2 involves the loss of basic peptides resulting in increased electrophoretic mobility for pepsin. Subsequent alkalinization results in loss of proteolytic activity. The 4 proteolytic constituents of human gastric mucosa were partially or completely separated by anion exchange chromatography. Each of these constituents demonstrated an increase in electrophoretic mobility following acidification. The speed and pH requirements of this change corresponded to that seen with activation of porcine pepsinogen. Realkalinization resulted in loss of proteolytic activity of all but one constituent. Three of the human pepsinogens were antigenic. An immunologic relationship was shown between the unacidified and the acidified antigens similar to that seen with the porcine pepsinogen-pepsin system. One human pepsinogen was immunologically related to purified porcine pepsinogen. These studies demonstrate that human gastric mucosa contains 4 physiochemi-cally and immunochemically distinct pepsinogens.