CARL F. CORI 



alternatives may be, rigorous proof for either concept has not 

 been obtained so far. 



Compartments of the Cell 



The control of rates of metabolism by intracellular enzymes 

 may be illustrated in the following examples. When isolated 

 frog muscle is compared at rest and during tetanic contraction, 

 a more than 1 00-fold difference in the rate of lactic acid forma- 

 tion can be demonstrated. The mechanism underlying this 

 increase in enzymatic rates has not been explained. Recent 

 work (9) indicates that at 0° C, even if there is no demon- 

 strable splitting of ATP or phosphocreatine during contraction, 

 there occurs nevertheless an increase in the concentration of 

 inorganic phosphate which may arise from an unknown precur- 

 sor. The concentration of inorganic phosphate in resting muscle 

 is high enough to saturate phosphorylase, the first enzyme in the 

 chain of reactions from glycogen to lactic acid. If the reaction 

 catalyzed by this enzyme were the rate-limiting step in glycolysis 

 in resting muscle, and if it were then accelerated 1 00-fold by the 

 formation of inorganic phosphate during contraction, one would 

 have to make the additional assumption that at rest the enzyme 

 is almost completely separated from inorganic phosphate. A 

 determination of intermediates of glycolysis in resting muscle 

 shows that hexosemonophosphate is present in a concentration 

 which would saturate phosphofructokinase. During contrac- 

 tion hexosemonophosphate increases (8), and in order to make 

 phosphofructokinase the rate-limiting step, the same additional 

 assumption would have to be made as in the case of phosphory- 

 lase — a compartment of the muscle cell which does not permit 

 contact between the enzyme and its substrate — a barrier which 

 is broken down during contraction and is re-established during 

 rest. Because of the possible existence of such barriers, it may 

 be misleading to draw conclusions from steady-state concentra- 

 tions of intermediates. For example, exposure of isolated frog 

 muscle to epinephrine causes an approximate doubling of the 



204 



