EFFECT OF DEFICIENCY IN MAN 



who made the further suggestion that the anti-anaemia factor in Hver 

 might be the product formed by the interaction of Castle's extrinsic 

 factor with the intrinsic factor of the ahmentary tract. This may be 

 absorbed from the intestine and stored in the livers of normal indi- 

 viduals, but not in the livers of patients with pernicious anaemia. 



Although the heptaglutamate is not converted into free folic acid 

 by the action of normal gastric juice, it is altered thereby and the 

 digested material did not yield free folic acid when incubated with 

 liver homogenate.^^" Gastric juice from pernicious anaemia patients, 

 on the other hand, had no effect on the heptaglutamate, whilst juice 

 from sprue patients behaved like normal gastric juice. Since pteroyl- 

 triglutamate produced reticulocytosis in cases of pernicious anaemia,^^^ 

 the effect of normal gastric juice on the heptaglutamate cannot be 

 simply to convert it into the triglutamate. It has also been shown ^^^ 

 that the normal gastric juice combines with vitamin B^g to give a 

 microbiologically inactive complex (page 543), whereas the gastric 

 juice from pernicious anaemia patients is inactive ; the latter appears 

 to be deficient in two respects therefore. It has been suggested that 

 apoerythrein, the factor in normal gastric juice that combines with 

 vitamin B^g, is Castle's intrinsic factor and vitamin B-^2 the extrinsic 

 factor and, in that event, it is possible that this reaction is essential 

 for the absorption and storage of vitamin B12, in the absence of which 

 folic acid is not liberated from the diet. 



That pteroylglutamic acid is necessary for the normal production 

 of red blood cells and the real operative agent that transforms a 

 pathological megaloblastic bone marrow into the physiological normo- 

 blastic state is suggested by the observations of Meyer et al.^^^ on the 

 effect of folic acid antagonists. They found that when a sufficient 

 amount of an antagonist was administered, together with liver extract, 

 the anticipated rise in red blood cells and haemoglobin did not occur ; 

 reticulocytosis was repressed and megaloblasts remained in the bone 

 marrow. The effect of vitamin B^g was also inhibited. 



Although the liberation of folic acid is therefore one of the functions 

 of vitamin B12, it does not appear to be the only one, since vitamin Bjg 

 and folic acid are not biologically equivalent. Thus, neither pteroyl- 

 glutamic acid nor its conjugate had a direct action on primitive 

 erythrocytes in vitro, whereas potent liver extracts caused them to 

 mature. ^^ Normal human and rat serum also contained the matura- 

 tion factor, whereas senrni from a pernicious anaemia patient did not. 

 Pteroylglutamic acid also failed to increase the maturation of bone- 

 marrow cells suspended in this deficient serum. 



It has also been suggested as an alternative theory that the 

 anti-pernicious anaemia factor is concerned with the synthesis of folic 

 acid in the body, but an objection to this is that purified liver extracts 



499 



