Fatty Acids Enter Cells by Simple Diffusion

Abstract

Juxtaposed in this issue of the Proceedings are two short reviews on the cellular uptake of water-insoluble substances, in this case, long-chain fatty acids. These reviews reflect two different biases as to how fatty acids and similarly apolar substances enter cells: whether by simple diffusion regulated by the physical chemical properties of water, the lipid bilayer region of membranes, and fatty acids, or by a facilitated mechanism dependent on specialized binding proteins and carrier proteins. The mechanism of cellular uptake of molecules like long-chain fatty acids has broad biomedical importance. Elucidation of the mechanism has implications for pharmacokinetics, for predicting the pharmacokinetic behavior of new compounds, and potentially for directing compounds of a given structure to selected kinds of membranes. Yet the current views of the problem could not be more divergent.

For example, a spontaneous mechanism for the uptake of the nonpolar compounds by cells predicts that solubility in plasma membranes and differential partitioning between these membranes and carrier proteins in blood, which are events independent of binding to proteins in membranes, is a primary determinant of rates of uptake into cells. The key, therefore, to directing compounds to selected tissues or to changing the rate of uptake in a given tissue, if the mechanism of uptake depends only on physical chemistry, is to understand the factors that modulate the solubility of apolar compounds in lipid bilayers. By contrast, the idea that cellular uptake of compounds like fatty acids occurs by biological mechanisms will lead the field into studies of the properties of specialized proteins.

There no longer are arguments about spontaneous generation; nor does anyone dispute the idea that the internal workings of cells can be approached and understood through reductionist experimental designs that depend on the rules of the physical sciences.