New concepts of cellular fatty acid uptake: role of fatty acid transport proteins and of caveolae.
Efficient uptake and channelling of long-chain fatty acids (LCFA) are critical cell functions. Evidence is emerging that proteins are important mediators of LCFA-trafficking into cells and various proteins have been suggested to be involved in this process. Amongst these proteins is a family of membrane-associated proteins termed fatty acid transport proteins (FATP). So far six members of this family, designated FATP 1-6, have been characterized. FATP 1, 2 and 6 show a highly-conserved AMP-binding region that participates in the activation of very-long-chain fatty acids (VLCFA) to form their acyl-CoA derivatives. The mechanisms by which FATP mediate LCFA uptake are not well understood, but several studies provide evidence that uptake of LCFA across cellular membranes is closely linked to acyl-CoA synthetase activity. It is proposed that FATP indirectly enhance LCFA uptake by activating VLCFA to their CoA esters, which are required to maintain the typical structure of lipid rafts in cellular membranes. Recent work has shown that the structural integrity of lipid rafts is essential for cellular LCFA uptake. This effect might be exerted by proteins, e.g. caveolin-1 and FAT/CD36, that use lipid rafts as platforms and bind or transport LCFA. The proposed molecular mechanisms await further experimental investigation.
Departments of Gastroenterology and Internal Medicine, University of Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany.
Jürgen
J
Pohl
Axel
A
Ring
Robert
R
Ehehalt
Thomas
T
Herrmann
Wolfgang
W
Stremmel
D018955:CD36 Antigens / Q000378:metabolism*; D022461:Caveolins / Q000378:metabolism / Q000502:physiology*; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding
D018955:CD36 Antigens; D022461:Caveolins; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D026901:Membrane Transport Proteins; C493568:SLC27A1 protein, human; C493573:SLC27A6 protein, human