CARBOHYDRATE METABOLISM OF THE ERYTHROCYTE 515 



the carbon monoxide and cyanide sensitivity of the respiration. Negelein 

 {2018) found that cyanide caused an increased production of lactic acid, and 

 Kiese and SchwartzkopfT {152Sa) found that hem/globin inhibits glycolysis. 

 The behavior of the oxidase toward inhibitors could also be explained on the 

 basis of the hypothesis that the oxidase is not cytochrome oxidase, but oxy- 

 hemoglobin, undergoing autoxidation to hem/globin; the latter is reduced to 

 hemoglobin by the reducing systems and is thus able to re-enter the cycle. 

 This hypothesis is supported by the work of Heubner and Kiese {1202a, 

 lo26,lo2Sa). Certain facts relating to it will be discussed in Section 4. It 

 must be pointed out here, however, that the presence of a complete respiratory 

 system in the erythrocyte would enable the erythrocyte to engage in a waste- 

 ful and useless oxidation of large quantities of glucose. The magnitude of 

 the respiration under the influence of substances such as methylene blue 

 indicates that, as far as the dehydrogenases and coenzymes are concerned, 

 the cell is relatively well equipped. It would seem a useful adaptation to 

 make use of the full capacity of these enzymes only when the physiologically 

 desirable reduction of hem/globin is to be brought about. 



Nonnucleated erythrocytes display aerobic glycolysis, the glycolytic 

 power varying considerably in different species. The breakdown of glucose 

 seems to follow a relatively normal path through phosphorylated inter- 

 mediates {706, 10I^6,126J^,18I^8,1932a,2208, 2209). Coenzymes I and II are 

 present. Adenosine triphosphate has long been known to be present {90Jf); 

 reticulocytes contain more of it than mature erythrocytes {2210). In the 

 absence of glucose, or when glycolysis is prevented by fluoride or by the 

 hemolysis of the cell, inorganic phosphate is set free {695). In the nucleated 

 avian erythrocyte, with an efficient respiratory system, there is no aerobic 

 glycolysis. 



In the presence of methylene blue or hemf'globin (methemoglobin) glucose 

 is broken down by the oxidation of hexose monophosphate to phospho- 

 hexonic acid, according to the work of Lipmann {1757), Warburg and Chris- 

 tian {2934,2935), and Dickens {588). The last author also showed that 

 phosphohexonic acid and ribose phosphate were further broken down. 

 Warburg and co-workers {2936,2942) showed that triphosphopyridine 

 nucleotide and a specific protein were required for the hexose monophosphate 

 system, but Kiese {1526) found that hemoglobin could not be reduced by 

 reduced triphosphopyridine nucleotide except in the presence of an addi- 

 tional protein, which he named hemoglobin reductase, and which appears to 

 be a flavoprotein. 



This is not the only system in the red cell which is able to reduce hemo- 

 globin. Wendel {3032,3033) and Shapot {2539) found a system which metab- 

 olizes lactate in dog erythrocytes, while Kiese {1526) has found it to be 

 present in guinea pig and horse erythrocytes. The hexose phosphate and 

 lactate reductions are probably caused by separate systems. Cox and Wendel 

 {508) consider that between "2.5 and 50% of the intracorpuscular reduction 

 of hem/globin is caused by lactate.* 



* Recently the reduction of hemoglobin in the red cell has been studied extensively 

 (c/. 993a,1071a,1262a,1530a,15.30b,2o28a,28,Ua). 



The reduction of hemOglobin caused by glucose is mainly due to the oxidation of 



