A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids

Lipids. 2001 Sep;36(9):981-9. doi: 10.1007/s11745-001-0809-2.


Fatty acids are the main structural and energy sources of the human body. Within the organism, they are presented to cells as fatty acid:albumin complexes. Dissociation from albumin represents the first step of the cellular uptake process, involving membrane proteins with high affinity for fatty acids, e.g., fatty acid translocase (FAT/CD 36) or the membrane fatty acid-binding protein (FABPpm). According to the thus created transmembrane concentration gradient, uncharged fatty acids can flip-flop from the outer leaflet across the phospholipid bilayer. At the cytosolic surface of the plasma membrane, fatty acids can associate with the cytosolic FABP (FABP(c)) or with caveolin-1. Caveolins are constituents of caveolae, which are proposed to serve as lipid delivery vehicles for subcellular organelles. It is not known whether protein (FABP(c))- and lipid (caveolae)-mediated intracellular trafficking of fatty acids operates in conjunction or in parallel. Channeling fatty acids to the different metabolic pathways requires activation to acyl-CoA. For this process, the family of fatty acid transport proteins (FATP 1-5/6) might be relevant because they have been shown to possess acyl-CoA synthetase activity. Their variable N-terminal signaling sequences suggest that they might be targeted to specific organelles by anchoring in the phospholipid bilayer of the different subcellular membranes. At the highly conserved cytosolic AMP-binding site of FATP, fatty acids are activated to acyl-CoA for subsequent metabolic disposition by specific organelles. Overall, fatty acid uptake represents a continuous flow involving the following: dissociation from albumin by membrane proteins with high affinity for fatty acids; passive flip-flop across the phospholipid bilayer; binding to FABP(C) and caveolin-1 at the cytosolic plasma membrane; and intracellular trafficking via FABP(c) and/or caveolae to sites of metabolic disposition. The uptake process is terminated after activation to acyl-CoA by the members of the FATP family targeted intracellularly to different organelles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • CD36 Antigens
  • Carrier Proteins / metabolism*
  • Caveolin 1
  • Caveolins / metabolism
  • Fatty Acid Transport Proteins
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Fatty Acids / metabolism*
  • Fatty Acids / pharmacokinetics
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Neoplasm Proteins*
  • Organelles / metabolism*
  • Organic Anion Transporters / metabolism*
  • Tumor Suppressor Proteins*


  • CAV1 protein, human
  • CD36 Antigens
  • Carrier Proteins
  • Caveolin 1
  • Caveolins
  • FABP7 protein, human
  • Fatty Acid Transport Proteins
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Neoplasm Proteins
  • Organic Anion Transporters
  • SLC27A1 protein, human
  • SLC27A6 protein, human
  • Tumor Suppressor Proteins