616 XIII. HEMOGLOBIN AND PORPHYRIN SYNTHESIS 



not suflBciently explain the high plasma iron level; iron is absorbed from the 

 intestine in increased amounts, or at least not in amounts decreased in 

 accord with the increased plasma level. There are some similarities of the 

 anemia caused by pyridoxine deficiency to pernicious anemia, in the increased 

 storage of iron, in the hyperplasticity of the bone marrow, and in neurologic 

 lesions. There is, however, no macrocytosis and no evidence for the increased 

 hemoglobin breakdown, which are found in pernicious anemia. In addition, 

 pernicious anemia is not cured by pyridoxine nor is the anemia of pyridoxine 

 deficiency cured by the antipernicious anemia principle. It appears that an 

 inhibition of hemoglobin synthesis and a failure of coordination between 

 hemoglobin synthesis and iron absorption both play a part. The prevention 

 of hemoglobin synthesis is evidently not due to an effect on iron mobiliza- 

 tion, nor does it appear to be due to an indirect effect on copper metabolism 

 {1821). Pyridoxine appears thus to be directly concerned with hemoglobin 

 synthesis. 



Pantothenic acid injected into eggs, or supplied to the hen, increases the 

 rate of hemoglobin formation in the chick (274o). 



Vitamin D improves the absorption of iron from the food, while it may 

 also act in part indirectly through an influence on the calcium and phos- 

 phorus metabolism io45,959; cf. Section 3.3.4.). Bile fistula dogs become 

 anemic unless bile acids are fed to them {2536,2731). Whipple and co-workers 

 {1194-) found that the bile fistula dog used iron fed per as inadequately for 

 hemoglobin synthesis, while iron injected parenterally was fully used. They 

 concluded from these experiments that bile acids were required for the 

 absorption of iron from the intestine. Feeding of bile acids did not restore 

 fully the ability of the animals to synthesize hemoglobin, and an additional 

 disturbance of liver function was assumed. Smith and Crandall {510,2578), 

 however, found no evidence for decreased absorption of iron from the intes- 

 tine. They attributed the anemia to a failure to absorb the reticulocyte- 

 ripening principle from the intestine. Recently Scott {2518) has shown that 

 fistula dogs receiving fat-soluble vitamins parenterally can be kept free from 

 anemia without bile therapy. Bile acids are therefore required for the absorp- 

 tion of these vitamins from the intestine. 



The "secondary anemia liver factor.'' Whipple and co-workers {2295,306^) 

 found that liver fed by mouth greatly increased the ability of their standard 

 anemic dogs to synthesize hemoglobin. This liver fraction (the "secondary 

 anemia liver factor") was different from the antipernicious anemia principle. 

 Its activity could also not be attributed to its iron content alone (of. also 

 m, 170, 1473,2859), although in human cases of vitamin deficiencies Moore 

 and co-workers {1980) found that iron alone was sufficient to cure the anemia. 

 The hemopoietic activity of the liver is clearly the sum of the activity of 

 iron, copper, various vitamins of the B class and probably still unknown 

 factors. Elvehjem and co-workers {1820) found liver almost, though not 

 fully, replaceable by synthetic vitamins of the B class {e.g., thiamine + 

 riboflavin + pyridoxine -|- pantothenate + choline + inositol) together with 

 bile salts, cysteine, xanthopterin, and asparagine. The riboflavin deficiency 

 of monkeys was cured much more effectively by liver than by riboflavin 

 {4S8), but Day and co-workers {54-7) found a combination of riboflavin, 



