Activation of pepsinogen (Pg) to pepsin (P) by intramolecular cleavage has been deduced from previous work. Inherent proteolytic activity of Pg after conformational change in acid solutions has been suggested. These experimental data suggest that Pg is chemically converted to P by assaying the potential proteolytic activity of Pg which remains after various times of activation. Pg activated for 1.5 min at pH 2.85 shows no initial difference spectrum when pH is adjusted to 7.2, as reported by McPhie. However, subsequent incubation at pH 8.5 gradually produces a difference spectrum similar to that of Pg versus P indicating a dissociation of denatured P and the activation peptide. The first order activation rate constant calculated from the change in the difference spectra is 0.43/min which agrees with the constant previously reported. The chemical conversion of Pg to P under these conditions is also demonstrated by quantitative analysis of the N terminal 2 residues of the Pg and P in the activation mixture, after the proteins have been separated from the activation peptides.
|Published - 1974