Figure 5.1. Function and subcellular location of fatty acid transport proteins, FABP, FATP/ACSVL, and ACBP in fatty acid transport and channeling.

The extracelluar concentration of fatty acids (FA) varies from 0.3 to up to 2 mM and they are largely bound to albumin (300–600 uM) at a ratio of 5–10 FA molecules per molecule of albumin. Cellular uptake of long-chain fatty acid (LCFA), very-long-chain fatty acid (VLCFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) occurs through three putative mechanisms: (1) FABPpm (FABPAST) localizes FA to the plasma membrane and CD36 fatty acid translocator facilitates transport across the phospholipid bilayer and is bound by FABPc (l-FABP), (2) FA can cross the membrane by simple passive diffusion or use a flip-fop mechanism resulting in donation of proton to the cytosol. The FA can be bound to 10 different FABPs or converted to FA-CoA by acyl-CoA synthetase (ACSL) to form an acyl-CoA ester, and finally (3) VLCFA are preferentially transported by one of five FATPs that because of their synthetase activity converts VLCFAs to VLC-acyl-CoA esters. In the cytosol, FA and FA-CoA esters are channeled to different organelles and metabolic pathways by FABP and ACBP. Different FABP, FATP, and ACBP show differential selectivity for FAs of different chain length and degree of unsaturation as well as vectorial channeling to different organelles for oxidation or synthesis of complex lipids. The plasma membrane FABPpm is identical to the mitochondrial membrane aspartate aminotransferase (AST) and ths is often identifed as FABPAST. Thus FABPpm has different functions depending on cellular location. Similarly, the cytosolic FABPc is also known as L-FABP and has two FA-binding sites, while other FABPs have a single FA binding site. (For color version of this figure, the reader is referred to the online version of this book).