120 FACTORS AFFECTING METABOLISM in vitro 



with the preservation of the ionic balance across nerve cell mem- 

 branes and the resulting increase in energy utilization directs 

 cellular metabolism towards a restoration of this balance. In this 

 scheme phosphoprotein is conceived as an intermediate being 

 broken down to yield inorganic phosphate and being rephos- 

 phorylated by phosphocreatine via the adenosine and guanosine 

 nucleotides. In such a sequence only the quantities of phospho- 

 creatine and inorganic phosphate need change in response to 

 stimulus, the quantities of the other three components remaining 

 constant, a situation w^hich has been found to be the case. It must 

 be admitted that since electrical stimulus has not yet been directly 



Phosphate 



Protein 

 GTP X 



/ Polarized 

 Protein / structure 



Electrical 



pulses 



Phosphoprotein Depolarized 

 structure 



Fig. 14. Diagram illustrating possible connexions between 

 energy-rich phosphates, phosphocreatine and electrical impulses. 



shown to alter the ionic balances of cerebral tissues this section of 

 the scheme must remain hypothetical. Nevertheless there seems 

 no reason to suppose that the physical changes involved in the 

 electrical stimulation of processes in the central nervous system 

 are likely to differ greatly from those involved in the stimulation 

 of peripheral nerve where the relationships between ionic balances 

 and state of excitation are better established (cf. Hodgkin, 1951; 

 Keynes, 1957). 



The placing of guanosine nucleotide as an intermediate between 

 adenosine triphosphate and the phosphoprotein was dictated by 

 the finding that the specific activity of the guanosine derivatives 

 increased whereas that of the adenine derivatives decreased when 

 the tissue was stimulated electrically. Guanosine triphosphate 

 could not therefore be phosphorylating adenosine diphosphate to 

 the triphosphate. A closer examination of this sequence has been 



