4 INTERMEDIARY METABOLISM AND GROWTH I 



polymers, starch and glycogen, represent primary sources of energy for the tissues 

 of animals and for many lower organisms, we shall begin by outlining the path- 

 ways of glucose catabolism. 



The first of these is the Embden-Meyerhof glycolytic sequence (Fig. i). In the 

 presence of the enzymes hexokinase and hexose isomerase, glucose is phos- 

 phorylated to glucose-6-phosphate and isomerized to fructose-6-phosphate. The 

 fructose-6-phosphate is then phosphorylated to fructose diphosphate and the latter 

 substance is cleaved in the presence of enzyme, aldolase, to two triose phosphate 

 molecules. The triose phosphates are oxidized to phosphoglyceric acid which is in 

 turn converted in a number of steps to pyruvic acid. Under anaerobic conditions, 

 many cells reduce pyruvic acid to lactic acid. Alternatively, the pyruvic acid may 

 be decarboxylated by yeast cells to acetaldehyde which is in turn reduced to 

 ethanol. The overall result is the conversion of one molecule of glucose to two 

 molecules of lactate or, in the case of the yeast cells, to two inolecules of ethanol 

 and two molecules of CO,. Carbons one and six of the original glucose molecule 

 are transformed to the beta carbons while carbons three and four give rise to the 

 carboxyl groups of the lactate molecules. Tumor tissues and many embryonic 

 tissues manifest an extremely high anaerobic glycolysis. Warburg (1956) has 

 pointed out that tumors derive a far greater proportion of their energy from the 

 glycolytic breakdown of carbohydrate than do normal tissues (see Chapter 12). 



Glucose-6-phosphate may also be derived from glycogen or starch. The enzyme, 

 phosphorylase, catalyzes the breakdown of glycogen and starch to glucose- 1- 

 phosphate. The glucose- 1 -phosphate may then be transformed to glucose-6- 

 phosphate, in a reaction catalyzed by the enzyme, phosphoglucomutase. 



2. The hexose inonophosphate shunt 



Alternatively, glucose may be catabolized via the "direct oxidative" or "hexose 

 monophosphate shunt" cycle (Racker, 1954; Horecker and Mehler, 1955). The 

 glucose must initially be phosphorylated to glucose-6-phosphate, as in the Embden- 

 Meyerhof sequence. However, the glucose-6-phosphate is then oxidized to 6- 

 phosphogluconic acid rather than isomerized to fructose-6-phosphate. 



Ribose-5-phosphate, acts as a catalyst in this metabolic cycle. As a result of the 

 cycle, one molecule of glucose is catabolized to three molecules of COj and to one 

 molecule of triose phosphate. The carbon dioxide molecules are derived from 

 carbon atoms one to three of the glucose molecule while carbon four of glucose 

 is converted to the aldehyde carbon of glyceraldehyde phosphate. The cycle is 

 shown in Fig. i and is summarized by the equations on page 5. Steps a) and b) 

 are mediated by TPN* requiring dehydrogenases. The product of step b) is a pentose 

 phosphate (Srere et al., 1955; Stumpfand Horecker, 1956). Steps d) and e) are 

 catalyzed by the enzymes, transketolase and transaldolase respectively (Horecker 

 et al., 1956a, b; Horecker and Smyrniotis, 1955; Racker, 1954; Horecker and 

 Mehler, 1955). Step g) is also catalyzed by the enzyme, transketolase, while steps h) 

 andf) are mediated by isomerase enzymes. The glyceraldehyde-phosphate which 

 arises from carbons 4-6 of the original glucose molecule may be further transformed 

 by glycolytic enzymes to pyruvate or lactate. 



