On the apparent inhibition of intramolecular activation of pepsinogen by pepsin substrates.
Marciniszyn et al. (Marciniszyn, J., Huang, J. S. Hartsuch, J. A., Tang, J. (1976) J. Biol. Chem. 251, 7095-7102) have recently suggested an intermediate in the intramolecular activation of pepsinogen. As evidence, they showed apparent competitive inhibition of activation by globin, indication a pepsinogen-globin complex. Previous work had shown pepsinogen activation to occur very rapidly in the presence of high concentrations of hemoglobin, a very similar pepsin substrate (McPhie, P. (1974) Biochem. Biophys. Res. Commun. 56, 789-792). This contradiction has been resolved by a re-evaluation of the techniques used in the two investigations. The experimental conditions of Marciniszyn et al. Were inadequately defined to ensure denaturation of pepsin, a prerequisite of their method. A small decrease in pH, caused by the presence of extraneous protein, prevents this denaturation and leads to consistent underestimates of the rate of zymogen activation.
On the apparent inhibition of intramolecular activation of pepsinogen by pepsin substrates. Marciniszyn et al. (Marciniszyn, J., Huang, J. S. Hartsuch, J. A., Tang, J. (1976) J. Biol. Chem. 251, 7095-7102) have recently suggested an intermediate in the intramolecular activation of pepsinogen. As evidence, they showed apparent competitive inhibition of activation by globin, indication a pepsinogen-globin complex. Previous work had shown pepsinogen activation to occur very rapidly in the presence of high concentrations of hemoglobin, a very similar pepsin substrate (McPhie, P. (1974) Biochem. Biophys. Res. Commun. 56, 789-792). This contradiction has been resolved by a re-evaluation of the techniques used in the two investigations. The experimental conditions of Marciniszyn et al. Were inadequately defined to ensure denaturation of pepsin, a prerequisite of their method. A small decrease in pH, caused by the presence of extraneous protein, prevents this denaturation and leads to consistent underestimates of the rate of zymogen activation.