Oxidative Pathways of Carbohydrate Metabolism 163 



is followed by decarboxylation; e.g. as indicated in Fig. 2, 

 where rapid fumarase action could produce labelling of both 

 C-2 and C-3 of malate and oxaloacetate. For example [2-^*C]- 

 pyruvate would then yield glucose labelled not only at C-2 and 

 C-5 but also at C-1 and C-2 as, in fact, occurs in liver. 



What, however, would occur in a tissue like muscle which is 

 very low in its content not only of G6P- and 6-PG-dehydro- 

 genases (Dickens and Clock, 1951; Clock and McLean, 1954) 

 but also has very little total TPN (Clock and McLean, 1955a)? 

 The answer has very recently been supplied by Hiatt and 

 co-workers (1958). In rat diaphragm, [2-^*C]pyruvate yields 

 on aerobic incubation glycogen labelled almost exclusively in 

 glucose carbons 2 and 5 (39 per cent and 55 per cent of total 

 ^*C, respectively). The conclusion seems inescapable that a 

 different mechanism operates in muscle from that which pre- 

 dominates in liver, and the results point to a direct type of 

 incorporation of pyruvate, suggested by Hiatt and co-workers 

 (1958) to be by reversal of the phosphopyruvate kinase 

 reaction. If this actually occurs, there must be a flaw in the 

 reasoning of Krebs and Kornberg (1957, p. 251) that impos- 

 sibly high ratios of ATP/ADP would be thermodynamically 

 necessary for such a direct reversal. 



One possible way out of this dilemma would be the "com- 

 partmentalization"* of this part of the ATP. Alternatively, 

 pyruvate could be converted to PEP by an oxido-reduction 

 mechanism. Such a reaction might be, e.g., the oxidation of 

 pyruvate to hydroxy pyruvate (or phosphohydroxy pyruvate, 

 in presence of ATP) with subsequent reduction to D-glycerate 

 (or phosphoglycerate) which could then enter the glycolytic 

 chain. It could be " resynthesized " to glucose or could pre- 

 sumably, via PEP, be carboxylated to OAA. Small quantities 

 of hydroxypyruvate are present in animal tissues according to 

 Linko and Virtanen (1955) and Holzer and Holldorf (1957). 

 An active glyceric acid kinase is known to be present in liver, 



* [At the suggestion of members of the symposium, the word "compart- 

 mentahzation" is replaced by " compartmentation " throughout this volume. 

 —Eds.] 



