36 Philip Siekevitz 



overshoot my mark, this will not happen in every case. I do 

 not know whether glucose gets into the cell as I have depicted, 

 by a pinocytic mechanism (Fig. 7) via the ER, as Holter and 

 his co-workers have indicated happens with amoeba. Mr. 

 Donald Young, in our laboratory, who has been working on 

 the whole problem of glucose exit and entry into the liver 

 cell as related to cell structure, has tried to show, by injecting 

 radioactive glucose and separating microsomes, that this 

 might also be the case for the liver, but without success. 

 Since there are many hazardous chances to be taken in this 

 sort of an experiment, we are not discouraged. However, it is 

 suggested that some, if not all, of the glucose gets into the 

 cell by passing into the ER after prior pinocytic entry, and 

 then passing through the ER membrane to be immediately 

 phosphorylated by ATP and hexokinase on the inner, cyto- 

 plasmic matrix, side of this membrane. The exit of glucose 

 is visualized as being accomplished by the exclusively micro- 

 somal enzyme, glucose-6-phosphatase, and thus the function 

 of this enzyme is thought to be that of secreting glucose into 

 the vesicles of the ER, and then out of the cell. Both of these 

 schemes take cognizance of the thought that glucose cannot 

 get in and out of the cytoplasmic matrix without coming into 

 contact with a transforming enzyme, hexokinase in the one 

 case and glucose-6-phosphatase in the other. Thus, a barrier 

 exists to the free interchange of intracellular and extracellular 

 glucose, considering the glucose in the ER lumina as extra- 

 cellular. This idea of the active transport of glucose through 

 cell membranes by the action of a phosphatase is not new (cf. 

 Danielli, 1952) and, in fact, has been successfully tested in the 

 yeast cell by Rothstein and his co-workers (Rothstein and 

 Meier, 1948; Rothstein, Meier, and Scharff, 1953) who found 

 that hexose phosphatase, as well as adenosine triphosphatase 

 (ATPase), are localized in the cell membrane, and by Sacks 

 (1944, 1945), who has postulated as a result of his experiments 

 that glucose-6-phosphate is formed in the muscle cell mem- 

 brane, and is split there, with glucose going into the cell and 

 phosphate remaining on the outside. What I further propose 



