Physical-chemical model for the entry of water-insoluble compounds into cells. Studies of fatty acid uptake by the liver.

The spontaneous transfer of water-insoluble substances from plasma to the interior of cells would involve a series of steps in which the substance of interest dissociates from albumin in plasma, enters the outer half of the plasma membrane of a cell, crosses the bilayer, and then dissociates from the inner half of the plasma membrane to enter cell cytosol and diffuses to sites of its metabolism. We have examined the behavior of long-chain fatty acids in the uptake process, assuming that none of these steps is facilitated by the cell during the entry of fatty acids into the liver. Comparison of the spontaneous rates for each individual step with rates of uptake of fatty acid by perfused liver leads to the conclusion that the uptake of fatty acids is not limited by kinetic factors but is determined instead by the equilibrium distribution (Keq) of fatty acids between albumin in plasma and the phospholipids of the plasma membrane. This idea was examined further by determining whether there was a relationship between the value for Keq and rates of uptake of a fatty acid and the pattern of kinetics for uptake. The data indicate that there is a linear relationship between Keq and the rate of uptake, that uptake rates can be predicted with a high degree of accuracy from thermodynamic data, and that the pattern of kinetics of uptake is compatible with the idea that the uptake rate is determined by the relative affinity of a fatty acid for albumin and membranes.