HANS KLENOW 



Recent studies of this alternative pathway have revealed the existence of a new 

 cycle for the oxidative breakdown of carbohydrates. This cyclic mechanism has been 

 established primarily by Horecker and his group, and has been formulated in the 

 following way (Horecker, 1953). 



In this reaction scheme the oxidation of glucose-6-phosphate to the S-lactone of 

 6-phosphogluconate is catalysed by Warburg's well-known Zjvischenferment. The 

 further breakdown of 6-phosphogluconate has been found to be an oxidative decarbo- 

 xylation leading to the formation of the five-carbon keto sugar ribulose-5-phosphate. 

 Both of these oxidation steps require triphosphopyridine nucleotide as hydrogen 

 acceptors. To account for the formation of ribulose-5-phosphate it has been postulated 

 that 6-phosphogluconate is first oxidized in the 3-position. A free 3-keto phospho- 

 gluconate has, however, not been isolated as an intermediate, and the possibility 

 exists that both oxidation and decarboxylation are catalysed by the same enzyme 

 as is the case with some other oxidative decarboxylations. The ribulose-5-phosphate 

 can be converted by a pentose phosphate isomerase to ribose-5-phosphate, a reaction 

 which is completely analogous to the interconversion of fructose-6-phosphate and 

 glucose-6-phosphate. These two pentose phosphate esters can now interact, and with 

 a highly purified enzyme the product has been shown in addition to glyceraldehyde- 

 3-phosphate to be a phosphate ester of the seven-carbon keto sugar, sedoheptulose. 

 This sugar was first isolated from the sedum plant, where it is present in large amounts 

 (La Forge and Hudson, 191 7). Recently Calvin and his group (Benson et al., 1951) 

 have found that sedoheptulose phosphate is one of the earliest products to be formed 

 during photosynthesis, a fact which is a further indication of its importance in the 

 intermediary metabolism. Glyceraldehyde-3-phosphate and sedoheptulose-7-phos- 

 phate can now further interact, and in the presence of the enzyme transaldolase the 

 products are fructose-6-phosphate and a tetrose phosphate. This reaction has been 

 proved to be a transfer of the three first carbons of sedoheptulose-7-phosphate, i.e. 

 the dihydroxyacetone group, to glyceraldehyde-3-phosphate, whereby fructose-6- 

 phosphate is formed by an aldole condensation. Fructose-6-phosphate is then con- 

 verted by hexose phosphate isomerase to glucose-6-phosphate, and we are back at 

 the starting-point of the cycle. Thus, with two turns of the cycle two moles of C0 2 

 are evolved, and four moles of triphosphopyridine nucleotide are reduced, which 

 will require two moles of 2 for oxidation. At the same time one mole of glucose-6- 

 phosphate is regenerated, and one mole of tetrose phosphate is formed. This tetrose 

 may, moreover, be further converted to hexose monophosphate by a mechanism not 

 yet completely clarified, whereby the cycle is completed (Horecker, 1953, Horecker 

 et al., 1954). It should furthermore be emphasized that all of the reactions of the 

 cycle have been shown to be reversible. The activity of some of the enzymes involved 

 in this scheme has been investigated in a variety of normal mammalian tissues and 

 in tumours (Glock and McLean, 1954), and the quantitative significance of the 

 oxidative pathway has been investigated with isotopically labelled compounds in 

 several organs (Bloom, Stetten and Stetten, 1953). 



This system of enzyme reactions then furnishes us with two processes for pentose 

 formation, i.e. the direct oxidation of glucose-6-phosphate to ribulose-5-phosphate 

 and ribose-5-phosphate, and the reaction between one molecule of glyceraldehyde- 

 3-phosphate and one molecule of sedoheptulose-7-phosphate leading to the formation 



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