VITAMINS 615 



The anemia caused by lack of riboflavin is hypochromic and microcytic 

 {1072,2599); cf however (4^8). Gybrgy and co-workers (1072) have specu- 

 lated that the function of riboflavin is the production of the correct arrange- 

 ment of amino acids for globin synthesis, but its necessity for respiration of 

 the primitive red cell appears to be a more likely explanation. 



In the case of ascorbic acid, its effect on red cell respiration and maturation 

 is only one of several attempted explanations of the microcytic anemia of 

 scurvy (Mettier and Chew, 1919; Minot and Castle, 1961; Menshikov, 1911). 

 Barron and Barron {177) showed that ascorbic acid given together with 

 cobalt prevents the appearance of polycythemia, and that it depresses the 

 polycythemia produced by previous cobalt administration. They found that 

 the respiration of the red cells of cobalt-polycythemic rabbits was greater 

 than normal, and that addition of cobalt to the same cells in vitro depressed 

 the respiration. They explained this by assuming that in consequence of the 

 cobalt inhibition of the respiration of the immature cells in the bone marrow, 

 these are thrown into the circulation at an earlier stage of development than 

 normal; when removed from the influence of cobalt, the respiration is that of 

 immature cells, and is subject to inhibition once again by in vitro addition 

 of cobalt. The effect of ascorbic acid on cobalt polycythemia was explained 

 by assuming that ascorbic acid binds cobalt and thus prevents its action. 



Davis {539) confirmed the results of Barron and Barron, but suggested an 

 alternative explanation for the action of ascorbic acid; he considers that this 

 substance has a normal action in increasing the respiration of the red cells, 

 this action being prevented by cobalt. 



Other authors consider ascorbic acid a regulator of hemoglobin synthesis 

 rather than of red cell maturation (Deeny, 550; Israels, 1892; MacFarlane, 

 181I^; Fokina, 911). This is supported by studies on iron metaboHsm, and 

 also by observations showing that deficiency of ascorbic acid and its subse- 

 quent replacement both affect the hemoglobin content of the blood more 

 rapidly than they do the erythrocyte count. Heilmeyer and Plotner {1221) 

 found that intravenous injection of iron ascorbate caused a greater increase 

 of hemoglobin formation than corresponded to its iron content. A mobiliza- 

 tion of iron from its depots may be assumed to account for this. MacFarlane 

 {1814) assumes that this mobilization in turn may be due to a reduction by 

 ascorbic acid of a ferric iron protein compound in the liver. This view agrees 

 with the more general scheme put forward by Granick {1034), in which he 

 assumes that the shift of ferric iron from ferritin is dependent on the Fe^"*" 

 ;=i Fe^+ equilibrium in the cell. In ascorbic acid deficiency the plasma iron, 

 but not the liver iron, is decreased (de Braganza and Saka, 327a). All these 

 investigations indicate that the primary action of ascorbic acid is on the 

 mobilization of depot iron; this may also occur in the mucosa of the ga.stro- 

 intestinal tract, facilitating iron absorption. 



Harrer and King {1131) found a moderate decrease of cytochrome oxidase 

 in guinea pig heart and muscle in scurvy, in spite of the increased metabolism 

 and tissue respiration; the significance of this observation is not yet clear. 



The predominant feature of the anemia caused by pyridoxine deficiency 

 is the hemosiderosis in spleen, liver, and bone marrow and the elevated 

 plasma iron {411,1821,3105). The lack of hemoglobin formation alone does 



