THE EXTERNAL SECRETION OF THE PANCREAS AS A WHOLE 1 99 



acid, free amino acids, lipoproteins and synthetically active enzymes. I 

 can imagine that through a special enzyme mechanism these parts may be 

 building new ribosomes step by step. This restitution de novo may be a 

 synthesis under controlling factors of the cell nucleus by the amount of 

 ribonucleic acid, extruded by the nucleolus [24, 25, 37]. 



The origin of enzymes in ribosomes of the pancreas has been proved 

 [32, 99, 102, 103, 106, 137, 139, 156 157, 171-177, 186, 202], and in many 

 other cells, shown at the first Symposium of the Biophysical Society [2, 3, 

 4]. The ribosomes have attained, in the last 2 years, a central position in 

 the metabolism of many different cells. It has been shown that these 

 ribosomes have a different ribonucleoprotein ratio : first in different cells, 

 secondly — and this is most important — in the same cell at different stages 

 of enzyme synthesis [171-175]- The ribosomes, which appear identical 

 under the electron microscope, are different biochemically. Step by step 

 the amount of ribonucleic acid decreases, but the amount of proteins 

 increases. 



2. What happens with these proteins synthezised in the ribosomes ? 

 From the investigations of Siekevitz and Palade [171 -177] and the Hokins 

 [77-87] it may be concluded that the proteins are released from the ribo- 

 somes and penetrate the wall of the endoplasmic reticulum by active trans- 

 port [71, 97, 129-139, 146, 149-15 1]. Inside the endoplasmic canals the 

 proteins may be stored for a short time as intracisternal granules. 



3. The intracisternal granules are found by Palade [136-139] in the 

 endoplasmic reticulum of the guinea-pig only i to 3 hr. after feeding, but 

 not earlier or later. They have a diameter of o • 20 • 3 ^ ; they are, therefore, 

 to be seen in the light microscope. They appear approximately homo- 

 genous inside the endoplasmic reticulum; they have no outer membrane, 

 and differ from the zymogen granules in several respects : {a) The intracis- 

 ternal granules originate inside the endoplasmic canals, while the zymogen 

 granules come from the vacuoles of the Golgi bodies, {h) They have a 

 diameter of at most 0-3 /t ; the zymogen granules, however, of o • 5 to 

 0-6 jtx. (r) They have no membrane; the zymogen granules, however, have 

 one. Thus it seems that the intracisternal granules and the zymogen 

 granules are not identical. But it is likely that both contain digestive 

 enzymes. 



4. Up to this stage of the secretion process I believe the sequence of 

 events on the assembly line has been settled to a certain degree. A further 

 series of arguments speaks in favour of a final condensation of the digestive 

 enzymes as zymogen granules in the vesicles of the Golgi bodies [66, 81, 

 119, 183]. Sluiter confirmed this condensation statistically using a periodic 

 count method by light microscope [185]. Also the experiments of Chesin 

 [19 21], Marshall [116], Farquhar and Wellings [42] made this conclusion 

 likely. The electron microscope showed a sequence of four different 



