ALKALINE PHOSPHATASE AND SECRETION 69 



that at many, if not all, sites of secretion of colloids, a high con- 

 centration of alkaline phosphatase is present. There were, how- 

 ever, many unsatisfactory features of this work. In the first 

 place, the fact that enzyme poisons which interfere with phos- 

 phorylating processes also prevent secretion does not necessarily 

 tell us very much about the actual process of secretion itself. 

 The general metabolism of the cell is also based on phosphoryla- 

 tion, and consequently failure of secretory activity as a result 

 of a poisoning of the phosphorylating mechanisms may simply 

 indicate a general breakdown in cellular activities. Secondly, it 

 was difficult to allot a function to alkaline phosphatase in con- 

 nection with secretion, since it is fundamentally a dephosphory- 

 lating enzyme. 



I pointed out in 1943 that, in any case, before a simple phos- 

 phorylating process can effect secretion it is necessary to have 

 specific phosphorylating and dephosphorylating enzyme systems 

 present in appropriate parts of cells. For example, for the secre- 

 tion of glucose from the kidney the requirements are those indi- 

 cated in Fig. 3. Consider the upper part of the figure, which il- 

 lustrates the necessary siting of various enzyme systems. Since 

 glucose phosphate permeates cells much more slowly than does 

 glucose, it is necessary to have a dephosphorylating system on the 

 external border of the tubule cells at A, so that any glucose phos- 

 phate in the tubule lumen is rapidly converted into glucose and 

 phosphate ion. The same difference between the permeabilities 

 of cells to glucose and glucose phosphate also determines the 

 intracellular siting of enzymes if secretion is to occur. If glucose 

 which has diffused into the tubule cells is converted immediately 

 into glucose phosphate, the tendency to diffuse back into the 

 tubule will be greatly reduced: consequently, a phosphorylating 

 system is required in the cytoplasm adjacent to the lumen at B. 

 The converse situation is required in the cytoplasm adjacent to 

 the tissue spaces: i.e., to accelerate passage through the cell mem- 

 brane glucose phosphate must be converted to glucose. Hence 

 there must be a dephosphorylating system at C. 



As a result of this distribution of enzyme systems, a pattern 

 of concentrations of glucose and glucose phosphate will be built 

 up as indicated in the lower part of Fig. 3. The net result of the 

 action of the enzyme systems is that, inside the cell, there is a 

 relatively high concentration of glucose against the membrane 



