22 METABOLISM IN THE NORMAL FUNCTIONAL STATE 



of phosphate metaboHsm. Views similar to these have also been 

 expressed by Vladimirov and Rubel (1955). 



Methods of calculation of the quantities of a phosphate renewed 

 in a given time can be made with some degree of precision only 

 if the specific radioactivities of the immediate stable precursor, as 

 well as the product, are known. Criteria involved in such calcula- 

 tions have been detailed by Zilversmit et al. (1943), and Hearon 

 (1951), and these criteria have not been fulfilled in experiments with 

 brain. Most calculations of rates of renewal of cerebral phosphates 

 appear to have been made on the basis of a simple multiplication 

 procedure. Even when this is not the case (Lindberg and Ernster, 



1950) the apparently insurmountable difficulties arising from the 

 differential rates of entry and metabolism of phosphorus makes the 

 accurate measurement of product-precursor relationships of the 

 type required a seemingly impossible task. Comparisons have 

 been made between the renewal rates of the acid-hydrolysable 

 phosphates of various tissues including brain by injecting radio- 

 active phosphate and subsequently analysing various organs for 

 adenosine triphosphate and phosphocreatine (Sacks and Culbreth, 

 1951). While these experiments also show that the acid-soluble 

 phosphates of brain exchange their phosphorus rapidly, they offer 

 no means of computing turnover rates and comparisons between 

 different organs are based on values which can have little real 

 meaning in this respect. 



These difficulties are not a drawback to the comparison of two 

 sets of data obtained in identical fashions when the results may be 

 expressed in terms of radioactivity relative to some standard of 

 comparison. In the case of the acid-soluble phosphates this 

 standard is usually the inorganic phosphorus of the brain since this 

 is the precursor of the other phosphates. Corrections for the blood 

 content (varying from 1 •3-6-0% according to the method of 

 obtaining the tissue) (Vladimirov, 1955; Dawson and Richter, 



1951) are necessary to obtain the most precise figures but this 

 correction is not always made. 



The experiments described above provided the first clear 

 demonstration that there was in brain a rapid metabolism of 

 phosphate in phosphocreatine, adenosine triphosphate and the 

 hexose monophosphates in vivo under unstressed conditions. Few 

 other phosphates in this group have been similarly examined. The 

 a-phosphorus of adenosine triphosphate was found to be renewed 



