METABOLISM IN THE NORMAL FUNCTIONAL STATE 15 



and include a significant proportion of uncharacterized substances 

 some of which fall into definite groups. Knowledge of their 

 metabolism has come mainly through measurements of the 

 amounts of radioactive phosphorus which is incorporated under 

 diflPerent conditions. Since the groups are heterogeneous it follows 

 that all members of any one group are not likely to be equally active 

 in this respect. 



Metabolism of Phosphorus 



Entry of Phosphorus to the Brain 



One of the simipler methods of studying the metabolism of 

 phosphorus compounds in an organ is by measuring the amount 

 of radioactive phosphate taken up in a given time. Such experi- 

 ments were delayed with brain since the entry of phosphorus is 

 very slow, giving rise to a belief that the bulk of the phosphorus 

 compounds in brain were very stable. Administration of radio- 

 active phosphate and subsequent analysis of the distribution in the 

 body organs showed that, in animals such as the mouse or rat, not 

 more than 0-1% of the original dose could be found in the brain 

 (Table 5). This value was not markedly exceeded at any time in 

 studies lasting up to 60 hr. It is now known that this is due to the 

 existence of a " blood-brain barrier " which is only slowly per- 

 meable to inorganic phosphate from the blood stream. Equili- 

 brium between the blood and brain inorganic phosphorus is a 

 process occupying several days. This is illustrated, for the mouse, 

 in Fig. 1 calculated from the data of Dziewiatkowski and Bodian 

 (1951). Equilibrium was not achieved for almost seven days, 

 thereafter the rate of decrease in activity in the blood exceeded that 

 in the brain. Similar slowness in attaining equilibrium has been 

 noted by other authors for the dog (Greenberg et al., 1943) and for 

 the chicken (Webster, 1954). 



Attempts to define the blood-brain barrier in terms of a single 

 anatomical structure have not met with success (Dobbing, 1956; 

 Brierley, 1957). Current thought tends to a description in which 

 permeability of the nerve cell membrane and metabolism play a 

 part (see Mcllwain, 1959). That phosphate entry to the brain is 

 regulated by metabolic processes similar to those excluding or 

 concentrating salts or specific carbohydrates is made more prob- 

 able by the recent work of Volkova (1957). Thus, raising the 



