Protein-Mediated Facilitated Uptake Processes for Fatty Acids, Bilirubin, and Other Amphipathic Compounds

Passage of various substances across cell membranes must be highly selective since it allows the cell to maintain a constant internal environment. Essential molecules such as glucose, amino acids, and lipids must be able to readily enter the cell, whereas waste compounds must leave the cell. This selective permeability of the plasma membrane is due to different transport proteins within the lipid bilayer (1). Those transporters can be roughly divided into pumps, carriers, and channels, each of which is characterized by their different ways of using energy and transporting solutes. In this article, we will focus on the transport of fatty acids, bilirubin and other amphipathic compounds such as bile acids and phospholipids which were long thought to enter cells by simple diffusion. We will start with describing fatty acid uptake as an example of receptor-mediated transport and will discuss the criteria by which active transport is distinguished from passive diffusion. In the following sections, discussion of the uptake of the other organic anions will be limited to a description of the isolated transport proteins. The mechanism of the translocation process of fatty acids through the plasma membrane is controversial. On the one hand, it is suggested that uptake represents passive diffusion and is only determined by the rate of metabolism (2-4). On the other hand, it is argued that translocation involves the interaction of specific receptors within the plasma membrane. The vast majority of experimental findings suggest that fatty acid uptake is protein facilitated. Before considering the actual process of fatty acid uptake, one should take into consideration how fatty acids are exposed to cells. As the major energy source of the organism, fatty acids circulate in the blood, where they are tightly bound to albumin which keeps them soluble.