Equilibration of pancratic digestive enzymes across zymogen granule membranes

Zymogen granules isolated from the rat pancreas released digestive enzyms in response to lowering the enzyme concentration of the medium in which the granules were suspended, and reabsorbed enzyme when the enzyme concentration of the medium was increased. The evidence suggests that the distribution of digestive enzyme between zymogen granule and medium is the result of an equilibrium process. This equilibrium is apparently expressed across the granule membrane since the disruption of the membrane barrier eliminated the delay in establishing new equilibrium between the bound and free enzyme. The release of enzyme was continuous (equilibration did not occur) when the suspending medium was continuously filtered, thereby maintaining a constant state of disequilibrium between intragranular enzyme and enzyme in the medium. The data suggest the following: (1) that digestive enzyme passes through the intact granule membrane bidirectionally, and (2) that there is a free cytoplasmic pool of digestive enzyme in intact cells which is in equilibrium with the enzyme content of the zymogen granule.