Is there facilitated uptake of fatty acids by the liver? Interpretation and analysis of experimental data

Abstract

Uptake of hydrophobic organic anions that are extensively bound to serum proteins has been a controversial issue for over 30 years. It is known that steady-state uptake is lower in the presence of binding proteins, but it is much higher than predicted on the basis of protein–ligand binding equilibrium. Several theories have been postulated to account for this observation. Recent work has shown how binding proteins are capable of enhancing the uptake rate of long-chain fatty acids by decreasing 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 accounts for all experimental data or whether hepatocytes facilitate the uptake of protein-bound ligands, by for example mediating the protein–ligand 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 these important metabolic substrates is vitally important in determining their overall utilization in a variety of clinical disorders as diverse as gallstones, obesity, and atherosclerosis.Key words: surface charge, pI, albumin, lysozyme, orosmucoid, α1-acid glycoprotein, protein binding, palmitate, organic anion, uptake, hepatocytes, facilitation, diffusion, unstirred fluid layer, myocytes, long-chain fatty acids, fatty acids.