GENERAL COMMENTS 159 



Phosphates as Regulatory Systems 



Evidence has been presented (p. 109) showing that the rates of 

 oxygen uptake by cerebral preparations iji vitro are governed both 

 by the quantities of inorganic phosphate and of an acceptor such as 

 adenosine diphosphate or creatine, which are present in the system 

 at any one time. Suggestions have been made as to how these may 

 operate in vivo. Thus, situations leading to a breakdown of 

 phosphocreatine, by increasing the levels of inorganic phosphate, 

 in turn permit metabolic activity and oxidative phosphorylation to 

 increase until such time as the initial equilibrium is restored. 

 Systems involving this type of change may therefore be regarded 

 as self regulatory ones, the " pacemaker " reaction of which is the 

 speed with which energy-rich phosphates are consumed. Viewed 

 in this manner it seems unnecessary to regard metabolism which 

 has been increased by various stimuli such as the addition of 

 potassium salts to the medium, as being anything other than the 

 speeding up of a metabolic process which is normally operating 

 below its maximum potential. 



Another " pacemaker " reaction involves the levels of oxidized 

 and reduced diphosphopyridine nucleotide in cerebral tissues. It 

 is well established that most of the energy-rich phosphate formed 

 during metabolism is derived during the oxidation of reduced 

 diphosphopyridine nucleotide and in normal tissues the ratio of 

 the amount of the reduced to the oxidized coenzyme at any given 

 moment, is likely to be a governing factor in the rate of this process. 

 Maintenance of levels of reduced diphosphopyridine nucleotide is 

 found to be assisted by the presence of an enzyme actively degrad- 

 ing the oxidized but not the reduced form of the nucleotide, thus 

 presumably serving to maintain cerebral oxidations at a high rate. 

 It might also be felt that a similar role could apply to the adenosine 

 triphosphatase of cerebral tissues. Thus, by increasing the 

 quantities of inorganic phosphate and adenosine diphosphate these 

 enzymes could conceivably increase the rate of cerebral metabolism. 

 There is little evidence either to suggest or deny such a role. It 

 has been suggested that the enzymes are in fact phosphokinases 

 transferring phosphate either from adenosine triphosphate to some 

 other substrate, or phosphorylating adenosine diphosphate to the 

 triphosphate in the intact tissue (Myers and Slater, 1957). 



