The influence of pteroylglutamic acid on glycine and on porphyrin metabolism.

In earlier communications we have presented evidence which we considered to be suggestive of a relationship between pteroylglutamic acid (PGA) or the antipernicious anemia principle and porphyrin metabolism (1,2). Some of the evidence has been indirect and not entirely convincing. However, the data in this communication offer unequivocal support to our hypothesis, and further provide insight into the mechanism of action of PGA in influencing the production of porphyrins. In a previous paper (3) it was implied that PGA may also influence the destruction of such porphyrin-containing compounds as hemoglobin, through its inhibitory action on certain flavin-containing enzymes. It has been shown by Shemin and Rittenberg (4) that portions of the glycine molecule are incorporated into the protoporphyrin of hemoglobin. Since rats excrete a considerable amount of protoporphyrin, which is thought to be produced in excess of their requirement for hemoglobin production (5), they are useful subjects for the study of porphyrin metabolism. In the present experiments the effect of PGA on porphyrin excretion has been studied with animals on a standard purified diet and on a purified diet containing sodium benzoate. Griffith (6) established that a reduction in the growth rate of rats follows the inclusion of sodium benzoate in their diets. This reduction was readily overcome by the addition to the diet of sufficient glycine to detoxify the benzoate. He also found that a partial restoration of growth on the benzoate-containing diets could be brought about by allowing the animals to have access to their feces or by increasing the amount of yeast used as a source of the vitamin B complex. In the present experiments the inclusion of PGA in the diets of sodium benzoate-fed rats was found to result