CHAPTER 4 



FACTORS AFFECTING PHOSPHATE 

 METABOLISM IN VITRO 



Of the numerous factors affecting the metabolism of cerebral 

 slices in vitro, those whose action upon phosphate metabolism 

 bear relationships to factors similarly active in vivo can be con- 

 veniently divided into two groups. In the first group are included 

 different oxidizable substrates and metabolic inhibitors. In the 

 second group, comprising factors whose action may be considered 

 primarily to be linked to physical changes, are included electrical 

 impulses and changes in the concentration of inorganic ions such 

 as potassium salts. Metabolic relations exist between both groups 

 but for the purposes of this chapter it is convenient to consider 

 them separately. 



Different Oxidizable Substrates 



It was seen in Chapter 3, that preparations of cerebral mito- 

 chondria were able to oxidize a wide variety of substrates, the 

 oxidation being accompanied by the phosphorylation of adenosine 

 derivatives to the triphosphate. However, although in the intact 

 slice the maintenance of adequate levels of energy-rich phosphates 

 might be expected to be supported by the oxidation of similar 

 substrates this has been found not to be the case. The quantities 

 of phosphocreatine and adenosine triphosphate maintained by 

 slices during incubation with different substrates vary widely 

 (Table 16). Of all the intermediates tested only pyruvate was 

 effective in supporting levels of phosphocreatine approaching 

 those found when glucose was the substrate, with citrate some- 

 what less effective. Fumarate, succinate and glutamate were 

 ineffective, and levels of adenosine di- and triphosphate were also 

 low. All the substrates supported an uptake of oxygen by the 

 tissue equal to or slightly greater than that found with slices 

 oxidizing glucose. It seems possible that the differences between 

 the ability to support oxidative phosphorylation in mitochondria 



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