248 GERTRUDE E. GLOCK 



I. Introduction 



The widespread distribution of the pentose sugars in Nature and the 

 important part they play as structural units of many essential cellular con- 

 stituents such as nucleic acids and coenzymes, makes the question of their 

 origin of considerable interest. Various methods of biosynthesis have been 

 suggested, but, according to our present state of knowledge, only two of 

 these appear to be of general biological significance. These are the hexose- 

 monophosphate oxidative pathway of carbohydrate metabolism (also 

 known as the "direct oxidative pathway" and the "hexosemonophosphate 

 shunt") and the enzymic condensation of C2 and C3 compounds. The oxi- 

 dative pathway leads to the formation of D-ribose-5-phosphate from d- 

 glucose-6-phosphate, whereas the condensation of C2 and C3 compounds 

 yields both pentoses and deoxypentoses and appears to be the only known 

 method of biosynthesis of deoxyribose. 



II. The Hexosemonophosphate Oxidative Pathway as a Source of 

 Pentose Phosphate 



1. Early Investigations 



The existence of a pathway, distinct from the glycolytic route, for the 

 oxidation of glucose-6-phosphate was first demonstrated in yeast extracts 

 by Warburg and his co-workers.^ - They found that the oxidation of hexose- 

 monophosphate by "Zwischenferment" (now called glucose-6-phosphate 

 dehydrogenase) was triphosphopyridine nucleotide (TPN) specific and, 

 using a purified dehydrogenase preparation,^ identified the oxidation 

 product as 6-phosphogluconate.2 Flavoprotein oxidase ("old yellow en- 

 zyme"), discovered^ and isolated^ in connection with these experiments, 

 was used to reoxidize the reduced TPN. Further oxidation of 6-phospho- 

 gluconate by yeast enzymes was also found to be coupled with TPN.^ 

 Lipmann,^ working with yeast macerates, suggested that 2-ketophospho- 

 gluconic acid would be the first oxidation product and considered that this 

 would yield arabinose-5-phosphate on decarboxylation. Dickens,^'* how- 

 ever, found that this pentose phosphate was neither oxidized nor fermented 

 by yeast extracts at a rate sufficient for it to be an intennediate in this 

 pathway, whereas D-ribose-5-phosphate was entirely suitable in this re- 



» 0. Warburg and W. Christian, Biocheni. Z. 254, 438 (1932). 



2 O. Warburg, W. Christian, and A. Griese, Biochem. Z. 282, 157, (19.35). 



3E. Negelein and W. Gerischer, Biochem. Z. 284, 289 (1936). 



^ O. Warburg and W. Christian, Biochem. Z. 266, 377 (1933). 



5 O. Warburg and W. Christian, Biochem. Z. 287, 440 (1936). 



6F. Lipmann, Nature 138, 588 (1936). 



7 F. Dickens, Biochem. J. 32, 1615 (1938). 



8F. Dickens, Biochem. J. 32, 1626 (1938). 



