Vitamin Interrelationships in Heme Synthesis

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Abstract
The rates of incorporation of glycine-2-C14 and of δ-aminolevulinic acid-2,3-C14 into heme in vitro by erythrocytes of young control ducklings increased in a straight line relationship with the reticulocyte count when the isotope incorporation was plotted against reticulocyte count. Extrapolation of the glycine line to zero reticulocyte concentration showed that essentially no glycine was incorporated into heme in the absence of reticulocytes. However, a significant incorporation of δ-aminolevulinic acid took place in the absence of reticulocytes, but increases beyond this minimum value were also parallel to the reticulocyte count. The relatively higher incorporation of δ-aminolevulinic acid than of glycine into heme by blood which was very low in reticulocytes could be attributed to this small utilization of ALA by mature cells. The incorporation of radioactive glycine and δ-aminolevulinic acid into heme in vitro was decreased in vitamin B6, niacin, pantothenic acid, riboflavin, and thiamine deficiencies, and this became more pronounced with the duration of the deficiencies. Glycine uptake was decreased more than δ-aminolevulinic acid uptake, and this was attributed primarily to low reticulocyte levels found in all the deficiencies. These effects made it difficult to determine whether or not the more efficient incorporation of δ-aminolevulinic acid could in part be attributed to a specific biochemical lesion involving the vitamin as an enzymatic cofactor in the synthesis of δ-aminolevulinic acid from glycine and succinate. That this was so in vitamin B6 deficiency was shown by the fact that the addition of pyridoxal phosphate stimulated the incorporation of glycine, but not of δ-aminolevulinic acid in vitro. It had no such effect in control blood.