Jejunal perfusion of simple and conjugated folates in tropical sprue

Absorption of labeled simple 3',5',9'-(3)H pteroylmonoglutamate, ([(3)H]PG-1) and conjugated pteroyl-mu[(14)C]glutamyl-gamma-hexaglutamate, ([(14)C]PG-7) folates was assessed in six patients with tropical sprue, before and after 6 mo of treatment, utilizing jejunal perfusion and urinary recovery techniques. Degradation products of [(14)C]PG-7 which were produced during perfusion were identified by DEAE-cellulose column chromatography. Jejunal mucosal activities of folate conjugase, lactase, sucrase, and maltase were measured in every patient. Malabsorption of both [(3)H]PG-1 and [(14)C]PG-7 was found in every untreated patient, with significant improvement after therapy. The urinary excretion of (3)H and (14)C paralleled the luminal disappearance of both isotopes. The chromatographic patterns of intraluminal degradation products of [(14)C]PG-7 obtained during perfusion did not differ from those previously found in normal subjects and were similar in studies performed before and after treatment. The activity of folate conjugase was increased in the mucosa of the untreated patients when compared to the post-treatment levels while the activities of mucosal lactase, sucrase, and maltase were originally low and increased significantly after therapy. These observations suggest that folate conjugase originates at a different mucosal locus than the brush border disaccharidases, and are consistent with previous evidence that folate conjugase is an intracellular enzyme. The present studies have demonstrated unequivocal malabsorption of both simple and conjugated folates in tropical sprue. In tropical sprue, folate malabsorption is the reflection of impaired folate transport and not of impaired hydrolysis.