516 XI. HEMOGLOBIN CATABOLISM, I 



In connection with the carbohydrate metaboHsm of the erythrocyte, 

 mention should also be made of the increase in respiration known as the 

 "Michaelis-Salomon eflfect," whicli is observed in the presence of glucose 

 when extracts of liver and other tissues are present (1940). This increase is 

 apparently not due to hemiglobin formation, and is inhibited by 10"^ M 

 cyanide, but not by carbon monoxide. The substance present in the extracts 

 is destroyed by acetone. The system has been further studied by Overbeck 

 (2095,2096) who concluded that the eflfect was due neither to a copper - 

 ascorbic acid -glutathione mechanism nor to the coupled oxidation of oxy- 

 hemoglobin. Instead he suggested that a flavoprotein was responsible. This 

 seems unlikely in view of the permeability of the cell wall and of the cyanide 

 sensitivity of the system. 



3.3. Other Reducing Systems in the Erythrocyte 

 3.3.1. Glutathione. The erythrocytes of many species contain consider- 

 able quantities of glutathione, the major part being in the reduced state 

 (2194,3120). Investigation has been stimulated by finding increases in blood 

 glutathione under conditions under which blood regeneration takes place 

 (111,254,963,1764,2020, in rabbit; 137,963,607, in man). The relation of 

 glutathione to nutritional anemia due to lack of copper (2180,2480) is dis- 

 cussed in Chapter XIII. 



The metabolism of glutathione in the erythrocyte was first investigated 

 by Meldrum (1900). He found that aeration of washed corpuscles results in 

 a slow diminution in the amount of reduced glutathione. The experiments of 

 Oberst and Woods (2iX)0a) actually show the same eflfect, although a dis- 

 appearance of total glutathione independent of aeration was also noticed on 

 incubation of cells. On storage of blood the reduced glutathione is even 

 slightly increased, while the glucose content diminishes (Bick, 256). 



Meldrum found that on aerobic incubation of washed cells a number of 

 sugars, among them glucose, were able to donate hydrogen for the reduction 

 of glutathione. He later (1902) showed that oxidized glutathione could be 

 reduced by the reconstructed hexose monophosphate dehydrogenase system. 



The actual function of glutathione in the mature erythrocyte is .still 

 obscure. A powerful glyoxalase system is present in the erythrocytes (1436, 

 1437), but in view of the fact that methylglyoxal is no longer considered to 

 play any role in the breakdown of carbohydrate, the function of the glyoxa- 

 la.se sy.stem remains unexplained. Since reduced glutathione is able to reduce 

 a number of protein disulfide linkages and, in addition, is able to protect 

 enzyme sulfhydryl groups from iodoacetate or trivalent arsenic compounds 

 (2143), it has been suggested that glutathione may be a general activator 

 for the oxidizable sulfhydryl groups in enzymes. The fact that triosepho.s- 

 phate dehydrogenase contains such groups (2207) suggests that glutathione 

 protects it in the erythrocyte. 



triose phosphate to phosphoglyceric acid, mediated by coenzyme I. Only in the 

 presence of methylene blue does the reduction by hexosemonophosphate, mediated 

 by coenzyme 11, become of major importance. Lactate is also oxidized by hemiglobin 

 to pyruvate; the proportion of hem?globin reduction due to this reaction difTers widely 

 in different species (c/. 1530). 



