24 Philip Siekevitz 



zymogen granules. By the coalescence of the membranes 

 surrounding the zymogen granules with the cell membrane, 

 the contents of the granules are pushed out into the pancreatic 

 ducts. Fig. 4 shows such a latter event in the process of 

 happening, while Fig. 9 shows the presence of the newly 

 synthesized secretory enzymes within the cavities of the ER 

 of the guinea pig pancreas, where they form intracisternal 

 granules. We can isolate these intracisternal granules and 

 have shown that they contain the same enzymes, and in the 

 same concentrations, as they are found in the isolated zymogen 

 granules (Siekevitz and Palade, 19586). Whether this trans- 

 porting process is peculiar to the pancreas, or is found in all 

 other tissues, like the glands or even the liver, which secrete 

 substances to the various extracellular fluids, is not known, 

 but Palay (1958) thinks it could well be a general process of 

 all cells. But more about this speculation later on. Incident- 

 ally, it might well be fortuitous that the microsomes have 

 become linked with protein synthesis in the minds of bio- 

 chemists ; most of the work has been done with liver and with 

 pancreas, and these are the organs par excellence which 

 secrete proteins. It could well be that ribonucleoprotein 

 particles are implicated in protein synthesis but in the liver 

 and pancreas these structures are attached to the ER mem- 

 branes, and the high rate of protein turnover of the micro- 

 somes is merely a reflection of the high rate of synthesis of 

 secretory proteins by those organs, the synthesized protein 

 being then secreted via the ER (cf. Howatson and Ham, 1957). 

 I have given a picture of what I believe to be the present 

 state of knowledge of the problem of the passage of molecules 

 into and out of the cell. Most of the initial examples have 

 dealt primarily, and necessarily, with large molecules, but 

 does the same viewpoint hold for smaller molecules, such as 

 the amino acids or glucose? We do not know, but let us con- 

 sider some schemes of various restricted parts of cellular 

 metabolism and see where it will lead us. Of course, this will 

 also have to do with the segregation of enzymes within the 

 cell; and mention should first be made of some observations 



