Abstract
The path of a small hydrophobic molecule through the aqueous cytoplasm is not linear. Partition may favor membrane binding by several orders of magnitude; thus significant membrane association will markedly decrease the cytosolic transport rate. The presence of high concentrations of soluble binding proteins for these hydrophobic molecules would compete with membrane association and thereby increase transport rate. For long chain fatty acid molecules, a family of cytosolic binding proteins collectively known as the fatty acid-binding proteins (FABP), ate thought to act as intracellular transport proteins. This paper examines the mechanism of transfer of fluorescent anthroyloxy-labeled fatty acids (AOFA) from purified FABP's to phospholipid vesicles. With the exception of the liver FABP, AOFA is transferted from FABP by collisional interaction of the protein with an acceptor membrane. The rate of transfer increased markedly when membranes contain anionic phospholipids; this suggests that positively charged residues on the surface of the FABP may interact with the membranes. Neutralization of surface lysine residues of adipocyte and heart-type FABPs decreased the AOFA transfer rate, and transfer was then found to proceed via aqueous diffusion rather than collisional interaction. Site-specific mutagenesis has further shown that the helix-turn-helix domain of the FABPs is critical for interaction with anionic acceptor membranes. In addition, direct interaction of adipocyte FABPs with anionic membranes has been demonstrated. Thus 'cytosolic' FABP may function in intracellular transport of fatty acids to decrease their membrane association, as well as to target fatty acids to specific subcellular sites of utilization.
Original language | English (US) |
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Pages (from-to) | 333-339 |
Number of pages | 7 |
Journal | Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology |
Volume | 115 |
Issue number | 3 |
DOIs | |
State | Published - 1996 |
Keywords
- anionic phospholipids
- binding proteins
- fatty acids
- fluorescent lipids
- lipid transport
- membrane-protein interactions
- membranes
ASJC Scopus subject areas
- Biochemistry
- Physiology