1. The administration of serine to seven patients with megaloblastic anemia due to sprue produced a suboptimal but definite reticulocytosis in four, and an equivocal reticulocyte elevation in two. It is believed that serine served as a formylating agent, leading to the formation of CF from THFA. Two subjects excreted normal quantities of folic acid in the urine during serine therapy.

2. The administration of histidine to one patient led to an excessive urinary excretion of FIGLU. Three other subjects with sprue excreted increased amounts of FIGLU in the urine without a prior loading dose of histidine.

3. Since the folic acid co-factors concerned with glycine and serine metabolism appear to function adequately in sprue patients, and since similar co-factors are concerned with histidine metabolism, the urinary excretion of FIGLU by these patients suggests an abnormality of the enzyme which converts FIGLU to glutamic acid (FIGLU transferase). Further studies will be necessary to clarify this inference.

4. The findings are discussed, and the view that folic acid may have a "pharmacologic" effect in certain forms of megaloblastic anemia is considered.

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