Figure 1. Model of long-chain fatty acid uptake in keratinocytes of the mammalian skin.

FAT/CD36 at the plasma membrane is hypothesized to bind to albumin-bound, longchain fatty acids and accelerate dissociation of fatty acids from albumin, generating high local concentrations of free fatty acids at the membrane. Fatty acids could then be translocated across the membrane via FATP1, -3, -4, or -6 (FATP1/3/4/6) by the vectorial acylation mechanism, whereby fatty acids are converted into acyl-CoA after import by the ACSVL activity of FATPs themselves, generating a gradient of free fatty acids across the membrane that drives further influx of free fatty acids. Fatty acids could also be imported by an unknown transporter (X1) on the plasma membrane, and converted into acyl-CoA by the FATPs located on the plasma membrane or on organellar membranes. Fatty acids in the cytosol could then be imported into various organelles for downstream metabolic pathways through unknown transporters (X2) on organellar membranes. FABP5 and ACBP bind to long-chain fatty acids and long-chain acyl-CoA, respectively, facilitating the intracellular trafficking of fatty acids.