Analysis of sequential events in intestinal absorption of folylpolyglutamate.
Although it is clear that the intestinal absorption of folylpolyglutamates is associated with hydrolysis to monoglutamyl folate, the precise sequence and relative velocity of the events involved in this absorption are not fully elucidated. In the present study, we used biosynthetic, radiolabeled folylpolyglutamates purified by affinity chromatography to analyze the relationship of hydrolysis and transport in rat jejunal loops in vivo. Absorption was best described by a series of first-order processes: luminal hydrolysis to monoglutamyl folate followed by tissue uptake of the product. The rate of hydrolysis in vivo was twice as high as the rate of transport. The latter value was identical to that measured for folic acid administered separately. The relevance of this sequential model was confirmed by data obtained using inhibitors of the individual steps in absorption of "natural" folate. Heparin and sulfasalazine were both effective in decreasing absorption. The former affected hydrolysis solely, whereas the latter acted as a competitive inhibitor of transport of monoglutamyl folate. These studies confirm that hydrolysis is obligatory and that the product is subsequently taken up by a transport process, common to monoglutamyl folates, that is the rate-determining step in transepithelial absorption.
Department of Medicine, University of Chicago, Illinois 60637.
B
B
Darcy-Vrillon
J
J
Selhub
I H
IH
Rosenberg
D000818:Animals; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006868:Hydrolysis; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism*; D007700:Kinetics; D011624:Pteroylpolyglutamic Acids / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D014316:Tritium
D011624:Pteroylpolyglutamic Acids; D014316:Tritium; D006493:Heparin; D005492:Folic Acid