IS THERE FACILITATED UPTAKE OF FATTY-ACIDS BY THE LIVER INTERPRETATION AND ANALYSIS OF EXPERIMENTAL-DATA

Uptake of hydrophobic organic anions that are extensively bound to ser um proteins has been a controversial issue for over 30 years. It is kn own that steady-state uptake is lower in the presence of binding prote ins, but it is much higher than predicted on the basis of protein-liga nd binding equilibrium. Several theories have been postulated to accou nt for this observation. Recent work has shown how binding proteins ar e capable of enhancing the uptake rate of long-chain fatty acids by de creasing the diffusional resistance of the unstirred fluid layer. The enhanced transport via codiffusion is especially important for tightly bound ligands like long-chain fatty acids. Whether this model account s for all experimental data or whether hepatocytes facilitate the upta ke of protein-bound ligands, by for example mediating the protein-liga nd dissociation rate, is not clear. We review the published reports to gain an understanding into the potential mechanism for the extraction of long-chain fatty acids. Understanding the uptake mechanism of thes e important metabolic substrates is vitally important in determining t heir overall utilization in a variety of clinical disorders as diverse as gallstones, obesity, and atherosclerosis.