Methaemoglobinaemia 



erythrocytes. Second, F. B. Straub 8 has isolated a protein from heart 

 muscle whose chemical behaviour is similar to that of coenzyme 

 factor I 9 . He has shown that the prosthetic group of this protein is 

 flavine-adenine-dinucleotide. One of our patients was given riboflavin 

 in large dosage (20 mg daily for a week) in the hope that synthesis of 

 coezyme factor might be favoured by a high concentration of the 

 vitamin in his blood. The level of MHb in the blood was not influenced 

 by this treatment 10 . The riboflavin was given intramuscularly, so that 

 the possibility of impaired intestinal absorption may be ruled out. 



It has been known for some time that certain dyestuffs capable of 

 undergoing reversible oxidation and reduction greatly accelerate the 

 rate of MHb reduction in vivo. This effect was also investigated, and 

 it was suggested that in the presence of methylene blue, the sequence 

 of reactions in the breakdown of glucose may follow the scheme of 

 F. Dickens 11 (see Figure 2, column B) and involve coenzyme factor II. 

 The cells from the cases appeared to be quite normal so far as this 

 series of reactions is concerned. It was concluded that coenzyme II 

 dehydrogenases could play only a subsidiary part in the normal 

 mechanism for the reduction of MHb, presumably because coenzyme 

 factor II did not react sufficiently rapidly with it. The observations of 

 M. Kiese and W. Schwartzkopff 12 on the effect of various combina- 

 tions of inhibitors on the reduction of MHb in intact red cells suggest 

 that the residual reduction in the absence of added substrate may be 

 due to reactions involving coenzyme II dehydrogenases, whose con- 

 tribution would then be about one-fifth of that of coenzyme I dehydro- 

 genases. This work and other work by Kiese 13 ' 14 on the mechansim of 

 MHb reduction in normal cells was carried out in Germany during 

 the recent war and was unknown to the Belfast workers. Where they 

 overlap, the two sets of experimental findings agree very closely. In 

 addition Kiese in detailed studies 13 succeeded in fractionating an 

 enzyme system capable of reducing MHb, and showed that a further 

 factor corresponding to coenzyme factor was required besides the 

 dehydrogenases and pyridine nucleotides. 



There are two main ways in which MHb may accumulate in the 

 blood : a It may be formed at a rate in excess of the reducing capacity 

 of the normal enzyme systems in the erythrocytes ; b there may be 

 some fault in the reducing mechanisms. The first group would include 

 the toxic methaemoglobinaemias such as those arising in the course 

 of treatment with sulphonamides, and also the interesting cases of 

 enterogenous cyanosis described by B. J. Stokvis 15 , A. A. H. van den 

 Bergh 16 and R. L. M. Wallis 17 . E. H. Fishberg 18 has recently 

 described a case of this kind, in which benzoquinoneacetic acid was 

 excreted in the urine. This acid was shown to be capable of forming 



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