FATTY-ACID TRANSFER FROM LIVER AND INTESTINAL FATTY-ACID-BINDING PROTEINS TO MEMBRANES OCCURS BY DIFFERENT MECHANISMS

Intestinal absorptive cells contain high levels of expression of two h omologous fatty acid-binding proteins (FABP), liver FABP (L-FABP), and intestinal FABP (I-FABP). Both bind long chain fatty acids with relat ively high affinity, The functional distinction, if any, between these two proteins remains unknown, It is often hypothesized that FABP are important in intracellular transport of fatty acids. To assess whether fatty acid transport properties might differ between the two enterocy te FABPs, we examined the rate and mechanism of transfer of fluorescen t anthroyloxy fatty acids (AOFA) from these proteins to model membrane s using a resonance energy transfer assay, The results show that the a bsolute rate of AOFA transfer from I-FABP is faster than from L-FABP. Moreover, the apparent mechanism of fatty acid transfer is different b etween the two proteins. The rate of AOFA transfer from I-FABP is inde pendent of ionic strength, directly dependent on the concentration of acceptor membrane vesicles, and dramatically regulated by the lipid co mposition of the membranes, These data strongly suggest that fatty aci d transfer from I-FABP to membranes occurs by direct collisional inter action of the protein with the phospholipid bilayer, In contrast, the characteristics of fatty acid transfer from L-FABP are consistent with an aqueous diffusion-mediated process, Thus the two enterocyte FABPs may perform different functions within the intestinal absorptive cell in the regulation of fatty acid transport and utilization. It is hypot hesized that L-FABP may act as a cytosolic buffer for fatty acids, mai ntaining the unbound fatty acid concentration, whereas I-FABP may be i nvolved in the uptake and/or specific targeting of fatty acid to subce llular membrane sites.