Methaemoglobinaemia 



The comparatively sluggish reaction between MHb and ascorbic 

 acid, as compared with the rapid enzymatic reduction with glucose 

 and lactate reported by Cox and Wendel 3 for dogs, suggested that 

 ascorbic acid does not normally play an important role in MHb 

 reduction in vivo, and prompted investigations into the enzymes in 

 the red cells of the cases, as well as a more detailed study of the reactions 

 taking place in normal red cells during the reduction of artificially 

 produced MHb. 7 The main conclusions regarding the normal 

 mechanism of reduction are summarized in column A of Figure 2. 

 The general idea advanced was that the limiting factor in the reduction 

 of MHb in normal cells is its reaction with coenzyme factor I 

 (diaphorase I), and that triosephosphate and lactate are the principal 

 substrates concerned. It was possible to assay the coenzyme factor I 



1 



A 

 Glucose 1 



I 



B 



Glucose 



2 Triosephosphate 



\ I 



\ Lactate 

 \ / 



3 Dehydrogenases 3 Dehydrogenases 



Hexosemonophosphate 



\ I 



JPhosphogl uconate 



. I 

 \\Pentosephosphate 

 \ \ / 



Coenzyme I 



4 Coenzyme II 



5 Coenzyme factor I 5 Coenzyme factor II 



T" I 



6 Methaemoglobin 6 Methylene blue 



I 



7 Methaemoglobin 



Figure 2. Diagrammatic scheme of the reactions 

 taking place in the reduction of MHb in erythrocytes. 

 Column A reactions occurring in the absence of 

 methylene blue ; B in the presence of methylene blue. 

 In cases of idiopathic methaemoglobinaemia where 

 there is a deficiency of coenzyme factor I, the re- 

 actions in column A do not occur, and MHb reduction 

 is very slow. 



activity of the erythrocytes and demonstrate a deficiency in the cells 

 from the cases {Figure 3). This deficiency appears to explain the 



225 



H— 15 



