Small Cytosolic Proteins Facilitate Movement of Fatty Acids

In order to be transported through the cell cytosol, free, or unesterified, fatty acids (those unlinked to CoA) are commonly bound by fatty acid–binding proteins (FABPs), which belong to a group of small cytosolic proteins that act as chaperones to facilitate the intracellular movement of many lipids. These proteins contain a hydrophobic pocket lined by β sheets (Figure 7-24). A long-chain fatty acid can fit into this pocket and interact noncovalently with the surrounding protein.

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FIGURE 7-24 Binding of a fatty acid to the hydrophobic pocket of a fatty acid–binding protein (FABP). The crystal structure of adipocyte FABP (ribbon diagram) reveals that the hydrophobic binding pocket is generated from two β sheets that are nearly at right angles to each other, forming a clam shell–like structure. A fatty acid (carbons yellow; oxygens red) interacts noncovalently with hydrophobic amino acid residues within this pocket. See A. Reese-Wagoner et al., 1999, Biochim. Biophys. Acta 23:1441(2–3):106–116.
[Data from Z. Xu, D. A. Bernlohr, and L. J. Banaszak, 1993, J. Biol. Chem. 268:7874, PDB ID 1lid.]

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The expression of cellular FABPs is regulated coordinately with cellular requirements for the uptake and release of fatty acids. Thus FABP levels are high in active muscles that are using fatty acids for generation of ATP, and in adipocytes (fat-storing cells) when they are either taking up fatty acids to be stored as triglycerides or releasing fatty acids for use by other cells. The importance of FABPs in fatty acid metabolism is highlighted by the observations that they can compose as much as 5 percent of all cytosolic proteins in the liver, and that genetic inactivation of cardiac muscle FABP converts the heart from a muscle that primarily burns fatty acids for energy into one that primarily burns glucose.