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

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Lipids

Abstract

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.

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Abbreviations

ACBP:

acyl-CoA binding proteins

ER:

endoplasmic reticulum

FABP c :

cytosolic fatty acid binding protein

FABPpm :

plasma membrane fatty acid binding protein

FAT:

fatty acid translocase

FATP:

fatty acid transport protein

mAspAT:

mitochondrial aspartate aminotransferase

PPAR:

peroxisome proliferator-activated receptor

VLDL:

very low density lipoproteins

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  1. Department of Medicine/Gastroenterology, Ruprecht-Karls-University, Bergheimer Str. 58, 69115, Heidelberg, Germany

    Wolfgang Stremmel, Jürgen Pohl, Axel Ring & Thomas Herrmann

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  1. Wolfgang Stremmel
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  2. Jürgen Pohl
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  3. Axel Ring
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  4. Thomas Herrmann
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Correspondence to Wolfgang Stremmel.

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Stremmel, W., Pohl, J., Ring, A. et al. A new concept of cellular uptake and intracellular trafficking of long-chain fatty acids. Lipids 36, 981–989 (2001). https://doi.org/10.1007/s11745-001-0809-2

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