Certain aspects of glycine and histidine metabolism in patients with sprue.

IT HAS BEEN BELIEVED that tropical sprue is caused by a primary folic acid deficiency,’2 although direct evidence in support of this concept is inadequate. While the administration of folic acid to patients with sprue in relapse will lead to clinical improvement, the remissions are often incomplete and malabsorption persists. Sprue may be conspicuously absent in the presence of gross vitamin and protein deficiencies,3 and on the other hand may appear among prosperous, well-fed persons.4 The irregular distribution of endemic sprue about the world has been the subject of comment.3’4 In a previous study5 it was found that tissue levels of folic acid appear to be only moderately reduced in Puerto Rican subjects with sprue in relapse. The concentration of folic acid in leukocytes was within the normal range in certain of the severely ill patients. In another study6 it was observed that such patients are capable of converting glycine to serine, a reaction which requires folic acid. It would appear then that the primary defect in the disease may be a disturbance in only certain of the several folic acid derivatives or in the enzymes for which they are the co-factors, rather than in the over-all quantity of folic acid. The investigations to be described rel)resent attempts to confirm previous studies and to localize further metabolic abnormalities in patients with sprue in relapse. The first approach was a clinical study concerning glycine-serine interrelationships which have been extensively studied from a biochemical point of view.7’4 According to Peters anti Greenberg’5 N10-hvdroxymethyl-THFA#{176} is the essential one-carbGn donor involved in the conversion of glycine to serine. Hydroxymethyl-THFA is derived from N’#{176}-formyl THFA ( heat-labile citrovorum factor ) by the reducing action of TPNH.’5 Albrecht and Bro(1Ui5t14’ have shown that HLCF occurs normally in human urine. The reactions may be summarized by the scheme shown in figure 1. In view of previous evidence that patients with sprue in relapse are capable of converting glycine to serine, it seemed theoretically possible to reverse