Oxidative Pathways of Carbohydrate Metabolism 167 



Determination of the relative importance of the 

 pentose phosphate and glycolytic pathways 



Various isotope methods have been devised for determining 

 the relative contributions of the pentose P and glycolytic 

 pathways to the total glucose catabolism of tissues involving 

 the use of glucose specifically labelled with ^*C in one or more 

 positions. Of these, the method most widely employed is to 

 determine the incorporation of C-1 and C-6 from [1-^*C]- and 

 [6-^ *C] -glucose into COg. In others, the incorporation of ^*C 

 into, e.g., lactate, fatty acids and acetoacetate is measured. 

 The validity of all these methods depends on two major 

 assumptions, firstly that recycling of hexose is not extensive 

 and secondly that there is rapid equilibration of triose 

 phosphates by triose phosphate isomerase. One of the im- 

 portant differences between these two types of method is that 

 in the latter the end product is formed after only relatively few 

 enzyme reactions. There are thus fewer opportunities for iso- 

 tope dilution and loss of isotope by side reactions than when 

 oxidation occurs via the complete glycolytic-tricarboxylic 

 acid sequence of events. 



Estimates of the relative contribution of the pentose P and 

 glycolytic pathways to the glucose metabolism of liver by 

 these two routes calculated from four different isotope 

 methods are shown in Table II. Although quantitative 

 evaluation is difficult and open to criticism (Wood, 1955) the 

 results for liver slices are in fairly good agreement and 

 indicate that 10-25 per cent of the glucose catabolized to the 

 particular end product being measured arises from the pentose 

 P pathway and 75-90 per cent from the glycolytic route. 

 A higher contribution of the pentose P pathway (an average 

 of approximately 40 per cent) was observed in experiments 

 with perfused rat liver (Murphy and Muntz, 1957) and after 

 intraportal injection of labelled glucose (Muntz and Murphy, 

 1957). This can probably be attributed to the fact that, in the 

 former experiments, the liver was perfused with a constant 

 physiological concentration of glucose since the blood was not 



