258 GERTRUDE E. GLOCK 



can operate serobically. Thus several workers have shown, ^^ using both 

 intact muscles and tissue slices, that, after glycolysis is inhibited by iodo- 

 acetate, oxidation of carbohydrate can still continue at a normal or only 

 slightly diminished rate. 



Oxidation of carbohydrate by the direct oxidative pathway proceeds in- 

 dependently of glycolysis since the primary oxidations of both glucose-6- 

 phosphate and 6-phosphogluconate are in general TPN-specific (cf. some 

 bacteria),^' '^^ show no requirement for either inorganic phosphate or ATP, 

 and are almost unaffected by concentrations of iodoacetate and fluoride 

 which completely inhibit glycolysis. ^^ Although this pathway is relatively 

 resistant to iodoacetate, liver 6-phosphogluconate dehydrogenase has been 

 shown to be a sulfhydryl enzyme^" and it is highly probable that this is 

 also true of glucose-6-phosphate dehydrogenase^" and pentose phosphate 

 isomerase." The formation of sedoheptulose-7-phosphate from pentose-5- 

 phosphate by spinach leaf preparations is also inhibited by sulfhydryl- 

 combining compounds.'^ 



The cyclic nature of the direct oxidative pathway has already been em- 

 phasized. The primary oxidation product of glucose-6-phosphate has been 

 shown by Cori and Lipmann^* to be 6-phospho-5-gluconolactone, the sub- 

 sequent hydrolysis to 6-phosphogluconate probably being spontaneous. 

 Oxidative decarboxylation of 6-phosphogluconate gives rise to ribulose-5- 

 phosphate (in equilibrium with ribose-5-phosphate), which is then degraded 

 into triose phosphate and a C2 fragment, and glucose-6-phosphate even- 

 tually resynthesized with the intermediate formation of sedoheptulose-7- 

 phosphate and fructose-6-phosphate. An important new development has 

 been the demonstration by Horecker that both formation of 6-phospho- 

 gluconolactone from glucose-6-phosphate-® and of ribulose-5-phosphate 

 from 6-phosphogluconate^* are reversible. Experiments of Cohen, however, 

 in which he determined the utilization of Ci-labeled gluconate by adapted 

 intact cells of E. coli, showed that the formation of 6-phosphogluconate 

 from glucose-6-phosphate is practically irreversible in this organism.^" 



The main reaction of these two alternative pathways of carbohydrate 

 metabolism, namely by the anaerobic glycolytic route and the direct oxi- 

 dative pathway are presented in Fig. 5, which also serves to emphasize 

 both their common origin in glucose-6-phosphate and their convergence 

 at triose phosphate. The relative importance of these two pathways under 



5« E. Shorr, Cold Spring Harb'or Symposia Quant. Biol. 7, 323 (1939); E. Stotz, Ad- 

 vances in Enzijmol. 5, 129 (1945). 



" B. Axelrod and R. Jang, Federation Proc. 12, 172 (1953). 



58 O. Cori and F. Lipmann, J. Biol. Chem. 194, 417 (1952). 



" B. L. Horecker and P. Z. Smyrniotis, J. Biol. Chem. 196, 135 (1952). 



60 S. S. Cohen, Nature 168, 746 (1951); in "Phosphorus Metabolism" (McElroy and 

 Glass, eds.), Vol. 1, p. 148. Johns Hopkins Press, Baltimore, 1951. 



