Autoactivation of pancreatic trypsinogen is controlled by carbohydrate-specific interaction

Activation of bovine pancreatic trypsinogen (BPTG) by trypsin (BPT) was found to be inhibited by D GalN/GalNAc at pH 5.5, the pH of secretory granules in the pancreas. Binding studies with biotinylated sugar-polymers indicated that BPTG and BPT bind to alpha-GalNAc, alpha-Man, and alpha-Gal better at pH 5.5 than at pH 7.5. Ultraviolet-difference spectra indicated that BPTG binding to alpha-GalNAc differs substantially from BPTG binding to other sugars. The N-alpha-benzoyl-D,L-arginine-p-nitroanilide hydrochloride- hydrolyzing activity of BPT was only slightly affected by these sugars. The results indicate that the binding of GalNAc - containing glycoconjugates protects BPTG from autoactivation, and this may be a self-defense mechanism against intrapancreatic activation. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.