Oleate uptake by isolated hepatocytes and the perfused rat liver is
competitively inhibited by palmitate.
Sorrentino, Dario, Decherd D. Stump, Karen Van Ness, Andr[acute]e
Simard, Andreas J. Schwab, Sheng-Li Zhou, Carl A. Goresky, and Paul
D. Berk.
Departments of Medicine (Division of Liver Diseases), Biochemistry,
and Surgery, Mount Sinai School of Medicine of the City University of
New York, New York, NY 10029, U.S.A.; McGill University Medical
Clinic, Montreal General Hospital, Montreal, Quebec H3G 1A4, Canada;
and Department of Internal Medicine, University of Udine, 33100
Udine, Italy
APStracts 2:0167G, 1995.
Competition for uptake between long chain free fatty acids has been
difficult to document because there has been no algorithm for
computing unbound concentrations of two fatty acids simultaneously in
solution with albumin. We modified an iterative procedure to permit
this computation, and studied initial [3H]-oleate uptake by isolated
hepatocytes and steady state uptake by the single pass perfused rat
liver from 600 [mu]M BSA solutions containing various concentrations
of oleate in the presence and absence of palmitate. In both systems,
Km was significantly higher in the presence of palmitate than in its
absence while Vmax was unaltered, indicating competitive inhibition.
In additional experiments employing the multiple transhepatic
indicator dilution technique, both the influx rate constant and
permeability surface product for oleate influx were significantly
reduced by palmitate, confirming that the competition observed in the
conventional perfused liver studies was at the influx step. Long
chain fatty acid uptake has now been shown to exhibit all the kinetic
properties of facilitated transport, and cannot be attributed solely
to passive diffusion.
Received 8 May 1995; accepted in final form 2 August 1995.
APS Manuscript Number G191-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.