Cell Structure and Metabolic Regulation 23 



the vesicular structures of the ER — are effectively out of the 

 range of intracellular enzymes? In other words, at the present 

 moment we are in confusion when we speak of intracellular 

 and extracellular, and, in truth, the descriptive value of these 

 terms has been greatly negated by the recent morphological 

 data and hence have no true meaning in a physiological sense. 



A more realistic picture of the way compounds get in and 

 out of the cell may be the following. Firstly, their importation : 

 undoubtedly, the cell concentrates and secretes molecules by 

 passage through the cell membrane, by some as yet unknown 

 means. However, it is now recognized that pinocytosis, the 

 bringing in of extracellular material by an engulfing or 

 invaginating mechanism of the cell membrane (Lewis, 1 OSS- 

 SB), is also a property of many cells. It has been beautifully 

 shown by Holter and his colleagues in the uptake of various 

 proteins, glucose and methionine by amoeba (Holter and 

 Marshall, 1954; Chapman-Andressen and Holter, 1955), and 

 at an electron microscopic level by Parks and Chiquoine (1956) 

 in the uptake of colloidal gold by phagocytes, by Wissig and 

 Palade (personal communication) in the uptake of ferritin 

 particles by capillaries (Fig. 8) and by Odor (1956) in the 

 uptake of thorium dioxide by the mesothelium of the mesen- 

 tery. The meaning of the implications derived from these 

 observations is obvious, and some biochemical ideas based 

 on these premises are developed below (p. 34). 



Similarly, the mechanism of secretion of intracellularly 

 formed compounds should also be looked at in this new light. 

 Palay (1958) and Palade and the present author (Siekevitz and 

 Palade, 1958a, b and c) have looked into the secretion and 

 prior formation of the zymogen granules of the pancreas, and 

 in these papers there is a good deal of morphological and 

 biochemical evidence that the seqretory enzymes are synthe- 

 sized at the site of the ribonucleoprotein (RNP) particles 

 attached to the ER membrane, that these enzymes are then 

 somehow pushed into the cavities, the intracisternal (luminal) 

 space, of the ER, and are then transported to the Golgi 

 region of the cell to be there packaged into the mature 



