154 F. Dickens, G. E. Glock and P. McLean 



respiratory chain will be considered by other contributors to 

 this symposium, and here it is merely noted that 15 equival- 

 ents of ATP could be formed in the operation of the Krebs 

 cycle proceeding from the level of pyruvate as far as its 

 complete oxidation in one turn of the cycle. The net result 

 is that per molecule of hexose completely oxidized, 32 moles 

 of ATP could be synthesized as compared with only 2 ATP in 

 the conversion of glucose to 2 moles of lactate. 



The Krebs cycle, therefore, provides the main energy source 

 of mammalian cells, especially when operating with the 

 glycolytic chain of reactions, since the carbohydrate com- 

 ponent of a normal diet generally provides the largest con- 

 tribution to the total energy source in the intact animal. The 

 individual stages of the Krebs cycle, providing a route for the 

 breakdown (and by producing necessary building materials 

 for the synthesis) of amino acids and fats, are also linked in an 

 essential relationship with the two other main groups of 

 foodstuffs and tissue metabolites. Except for the isocitric 

 stage [and even this may be mainly through DPN in mito- 

 chondria (Ernster and Navazio, 1957)] the oxidation of 

 carbohydrate by this route is by DPN systems and differs 

 essentially in this respect from the exclusively TPN-linked 

 animal phosphogluconate pathway, to be discussed below. 



The glucuronate pathway 



Although this recently discovered pathway is not at present 

 considered to have great quantitative importance, it is briefly 

 mentioned here as being the pathway of biosynthesis of 

 ascorbic acid and of the urinary L-xylulose excreted in cases 

 of congenital pentosuria, usually in amounts of from 2-5 g./day 

 (Enklewitz and Lasker, 1933). Both of these metabolites are 

 now believed to be derived from glucuronic acid (or its 

 lactone), the most probable source of which is, as shown in 

 Fig. 1, from GlP reacting with UTP to form UDP-glucose. 

 This uridine nucleotide of GlP can be oxidized at the C-6 of 

 glucose by a two-stage DPN oxidation (Strominger et aL^ 



