Oxidative Pathways of Carbohydrate Metabolism 153 



stages for the resynthesis of glycogen from blood lactate or 

 pyruvate, this function being especially important in liver, 

 which according to the well known Cori cycle (Cori, 1931) is 

 the tissue mainly responsible for this resynthesis. The tissue 

 localization of G6Pase, which is active in liver but absent 

 from muscle (Fantl, Rome and Nelson, 1942; Swanson, 1950) 

 prevents breakdown to blood glucose of this intermediate in 

 muscle. 



The pyruvate formed in the E-M pathway stands at one 

 of the most important key-points in determining the subsequent 

 route (Figs. 1 and 2). This can be reductive to lactate; a 

 reaction which predominates anaerobically with concomitant 

 reoxidation of the DPNH formed in the glyceraldehyde 

 phosphate oxidative stage. Aerobically, oxidative decarboxy- 

 lation can yield acetyl coenzyme A (acetyl CoA) which can 

 either undergo condensations and reductions to fatty acids or 

 be oxidized via the Krebs tricarboxylic acid cycle to CO2 and 

 water; which route is followed depends initially on the amount 

 of acetyl CoA available in relation to the oxaloacetate and to 

 the energy requirements (see Krebs and Romberg, 1957, for a 

 full discussion). The levels of oxidized DPN+ and TPN+ (the 

 latter for the i^ocitric dehydrogenase reaction) and of their 

 respective cytochrome c reductases must also be important 

 in favouring a Krebs cycle pathway. The main aerobic 

 source of energy in animal tissues is via this route, being 

 associated primarily with the oxidative decarboxylations of 

 pyruvate, i^ocitrate and a-ketoglutarate and the dehydro- 

 genations of succinate and malate. 



Whereas the glycolytic enzymes (like those of the pentose 

 phosphate pathway described below) are located in the soluble 

 fraction of the cell, the Krebs cycle system appears to be 

 localized in the mitochondria, together with the cytochrome 

 electron transport system. Oxidative phosphorylations accom- 

 panying the oxidation of DPNH produced in the above 

 reactions can proceed at the maximum rate of 3 moles ATP 

 synthesized per atom of oxygen transported (Lehninger, 

 1955). The detailed nature of these stages in the oxidative 



