IDENTIFICATION OF A PEPTIDE RELEASED DURING AUTOCATALYTIC ACTIVATION OF TRYPSINOGEN

Abstract

In the presence of calcium ions, at pH 8, reaction (b) is suppressed and the conversion of the zymogen to the active enzyme is essentially complete. Until recently, little was known of the chemical changes accompanying this conversion. Within the limits of the experimental errors of sedimentation and diffusion measurements, trypsinogen and trypsin have identical molecular weights (4, 5), suggesting that no large fragments arise from the proteolytic activation by trypsin. Rovery, Fabre, and Desnuelle (6) reported valine to be the single N-terminal group of trypsinogen, and isoleucine to occupy the same position in DIP-trypsin.1 Both proteins were found to be unreactive toward carboxypeptidase (7), suggesting that any C-terminal group which may be present is the same in both proteins. The replacement during activation of the N-terminal valine by isoleucine indicates that 1 or more peptide residue has been removed from the single polypeptide chain of trypsinogen. Evidence for the appearance of an activation peptide has been obtained in the course of this work and has led to its isolation and chemical characterization, as reported in this communication.