Enzymes 65 



apparently due to absence of the flavoprotein enzyme in red cells 

 that normally reduces methaemoglobin with the aid of reduced 

 DPN as a hydrogen donor. 



A somewhat more complicated picture is presented by Favism. 

 Here there is a genetically determined sensitivity to the haemolytic 

 action of the Fava bean. The disease is apparently due to a con- 

 genital absence from the red cell of the enzyme glucose-6-phosphate- 

 dehydrogenase which is part of the "shunt" pathway of glycolysis 

 (See Fig. 5). The activity of this enzyme is a major source of reduced 

 TPN and absence of the enzyme leads therefore to deficient produc- 

 tion of reduced TPN, which is associated in turn with a decline in 

 the concentration of reduced glutathione in the red cell due to lack 

 of available hydrogen ions. A fall in the level of this last substance 

 is associated with abnormal sensitivity to haemolysis. Two possible 

 explanations of this effect are that reduced glutathione, apart from 

 being a general protector of enzymes susceptible to inactivation by 

 oxidation, is required in glycolysis, being a coenzyme for triosephos- 

 phate dehydrogenase and hence for the synthesis of ATP, the chief 

 energy source for the exclusion of water and sodium by the red cell. 

 Abnormal entry of water and sodium is of course attended by 

 haemolysis. Familial sensitivity to primaquine and naphthalene has 

 a similar basis to Favism. In both cases glucose-6-phosphate-de- 

 hydrogenase is absent from the red cells although not from other 

 tissues. The detailed mechanism of Favism and similar conditions 

 is not altogether clear. It seems likely, however, that reduced 

 glutathione protects against the haemolytic properties of certain 

 agents and that its deficiency (due to absence of glucose-6-phos- 

 phate-dehydrogenase) is a central feature of this group of diseases. 



B. Genetically Determined Enzyme Deficiencies in the 

 Synthesis of Hormones 



Goitrous cretinism is a congenital form of hypothyroidism 

 usually associated with enlargement of the thyroid gland. It is due 

 to a genetically determined failure to synthesise thyroid hormone 

 following absence of one of at least three enzymes. The deficiency 

 may be in the oxidase that converts inorganic iodide to iodine; in 



