Cell Structure and Metabolic Regulation 41 



become bound to cell structural elements. It is a different 

 matter when we think of how this binding can be regulated. 

 Piling hypothesis upon hypothesis, I would suggest that the 

 hormones somehow control this movement of enzymes within 

 the cell. Thus, the hormones involved in carbohydrate 

 metabolism are depicted as mot acting on the enzyme per se 

 but in bringing enzyme, substrate, and cofactors together at a 

 suitable surface, and they do this by the actual moving of the 

 enzyme, complexing it perhaps, to the site where the sub- 

 strate and cofactors are at the membrane surface. Even 

 though we could not show it with the binding of hexokinase 

 to mitochondria, it is still possible that insulin could act in 

 such a manner to bind hexokinase to the ER membranes and 

 thus increase its activity. In the present fragmented state of 

 our knowledge one can only talk in general terms, but it is 

 hoped that this discussion will give rise to specific experi- 

 ments and to more definite conclusions. 



I would like to end this presentation by citing some recent 

 work which I think signifies more than we can guess at present; 

 for I can give you a rousing climax to this sort of paper only 

 by ending with a question mark. The ribonucleoprotein 

 particles which can be detached from the microsomes of the 

 pancreas still contain the enzymes which we think are synthe- 

 sized at this site, such as amylase, ribonuclease (RNAase), 

 chymotrypsinogen and trypsinogen (Siekevitz and Palade, 

 19586 and c). These enzymes are firmly attached to these 

 particles, for they cannot be washed out with water or even 

 with low concentration of DOC. We have no conclusive 

 evidence at present that these enzymes are not non-specifically 

 adsorbed onto the particles, but we are assuming for the 

 present that they are specifically bound to these synthetic 

 sites. However, as Table VII shows, these enzymes — and 

 RNAase and chymotrypsinogen have been tested as well as 

 amylase — do become detached if the particles are treated with 

 5 X 10~* M-ATP or inorganic pyrophosphate. Inorganic 

 phosphate and AMP will do the same but only at ten to twenty 

 times higher concentrations. Mg2+ at low concentrations 



