278 A SYMPOSIUM ON RESPIRATORY ENZYMES 



PATHWAYS OF CARBOHYDRATE METABOLISM 



E. S. GUZMAN BARRON 

 University of Chicago 



Whether the metabohsm of carbohydrates by animal tissues is 

 always accomplished according to Embden-Meyerhof's and Cori's 

 schemes of phosphorylations and oxidation-reductions has not yet 

 been established. In fact, if the normal pathway is obstructed, the 

 breakdown of carbohydrates might proceed through other pathways. 

 Direct oxidation of glucose, of hexosemonophosphate, and of phos- 

 phoglycerate might be the accessory pathways, although none of 

 these has yet been shown to occur in animal tissues. The oxidation of 

 a single substance may proceed via different enzyme systems; thus 

 in sea urchin eggs (with no succinodehydrogenase and no cyto- 

 chromes) the metabolism of carbohydrates undoubtedly proceeds 

 through different pathways than in sperm (with succinodehydro- 

 genase and cytochromes). The interesting findings of Korr (oxida- 

 tions not inhibited by azide in resting cells and inliibited by azide 

 when the cells are in active work) can be presented as examples in 

 favor of this opinion. 



The existence of these multiple pathways makes possible the 

 orientation of reactions which occur continually in living cells, the 

 metabolism of pyruvate being the clearest example. This is illus- 

 trated in the scheme shown on page 279 in which only the pertinent 

 steps are reproduced. 



Pyruvate is an extremely reactive substance, and seventeen differ- 

 ent pathways of its metabolism are known to exist in living cells. 

 In animal tissues, in the absence of oxygen, part of the pyruvate 

 formed during the breakdown of carbohydrate is reduced by dihy- 

 drodiphosphopyridine nucleotide (Py(P04)2Ho) to lactate, a reac- 

 tion the extent of which represents the degree of anoxia; part of it 

 may be reduced to alanine (Warburg and Christian's d-amino acid 

 oxidase) or may be used for transaminations or dismutations. In the 

 presence of oxygen, pyruvate activated by diphosphothiamine- 

 protein may be oxidized to acetylphosphate; may, through conden- 

 sation reactions, be responsible for the synthesis of alpha-ketoglu- 

 tarate, cisaconitate, acetoacetate, acetylmethylcarbinol, or carbo- 

 hydrate. It might, as postulated by Wood and Werkman, combine 

 with carbon dioxide to give oxalacetate, an important reaction still 

 eluding direct demonstration, which is the base of many hypotheses 

 for the breakdown and synthesis of carbohydrate. Oxalacetate 

 formed in this way may be reduced by Py(P04)8Hg to malate, thus 



