How are free fatty acids transported in membranes? Is it by proteins or byfree diffusion through the lipids?

Although transport of long-chain free fatty acids (FFAs) into cells is ofte n analyzed in the same way as glucose transport, we argue that the transpor t of the Lipid-soluble amphipathic FFA molecule must be viewed differently The partitioning of FFAs into phospholipid bilayers and their interfacial i onization are particularly relevant to transport. We summarize new data sup porting the diffusion hypothesis in simple lipid bilayers and in plasma mem branes of cells. Along with previous supporting data, the new data indicate that transport of FFAs through membranes could occur rapidly by flip-flop of the un-ionized form of the FFA. It appears that, at least for the adipoc yte, passive diffusion guarantees fast entry and exit of FFAs at both low a nd high concentrations. Although there are several candidate proteins for t he membrane transport of FFAs, most of these proteins have other establishe d functions. Thus, unlike the glucose transporters, these proteins would no t be single-function proteins. Definitive proof of their function as FFA tr ansporters awaits their reconstitution into simple model systems.