OLEATE UPTAKE BY ISOLATED HEPATOCYTES AND THE PERFUSED-RAT-LIVER IS COMPETITIVELY INHIBITED BY PALMITATE

Competition for uptake between long-chain free fatty acids has been di fficult 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 comput ation and studied initial [H-3]oleate uptake by isolated hepatocytes a nd steady-state uptake by the single-pass perfused rat liver from 600 mu M bovine serum albumin solutions containing various concentrations of oleate in the presence and absence of palmitate. In both systems, t he Michaelis-Menten constant was significantly higher in the presence of palmitate than in its absence, whereas the maximal reaction velocit y was unaltered, indicating competitive inhibition. In additional expe riments employing the multiple transhepatic indicator-dilution techniq ue, the influx rate constant and permeability-surface area product for oleate influx were significantly reduced by palmitate, confirming tha t the competition observed in the conventional perfused liver studies was at the influx step. Long-chain fatty acid uptake has now been show n to exhibit all the kinetic properties of facilitated transport and c annot be attributed solely to passive diffusion.