Transfer of fatty acids between intracellular membranes: roles of soluble binding proteins, distance, and time

Soluble fatty acid binding proteins (FABPs) are thought to facilitate exchange of fatty acids between intracellular membranes. Although many FABP variants have been described, they fall into two general classes. "Membrane-active" FABPs exchange fatty acids with membranes during transient collisions with the membrane surface, whereas "membrane-inactive" FABPs do not. We used modeling of fatty acid transport between two planar membranes to examine the hypothesis that these two classes catalyze different steps in intracellular fatty acid transport. In the absence of FABP, the steady-state flux of fatty acid from the donor to the acceptor membrane depends on membrane separation distance (d) approaching a maximum value (J(max)) as d approaches zero. J(max) is one-half the rate of dissociation of fatty acid from the donor membrane, indicating that newly dissociated fatty acid has a 50% chance of successfully reaching the acceptor membrane before rebinding to the donor membrane. For larger membrane separations, successful transfer becomes less likely as diffusional concentration gradients develop. The mean diffusional excursion of the fatty acid into the water phase (d(m)) defines this transition. For d<<d(m), dissociation from the membrane is rate limiting, whereas for d>>d(m), aqueous diffusion is rate limiting. All forms of FABP increase d(m) by reducing the rate of rebinding to the donor membrane, thus maintaining J(max) over larger membrane separations. Membrane-active FABPs further increase J(max) by catalyzing the rate of dissociation of fatty acids from the donor membrane, although frequent membrane interactions would be expected to reduce their diffusional mobility through a membrane-rich cytoplasm. Individual FABPs may have evolved to match the membrane separations and densities found in specific cell lines.