AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 3 361-G366, Copyright © 1988 by American Physiological Society
Analysis of sequential events in intestinal absorption of folylpolyglutamate
B. Darcy-Vrillon, J. Selhub and I. H. Rosenberg
Department of Medicine, University of Chicago, Illinois 60637.
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.
