INTRACELLULAR LIPID-BINDING PROTEINS AND THEIR GENES

Intracellular lipid-binding proteins are a family of low-molecular-weight single-chain polypeptides that form 1:1 complexes with fatty acids, retinoids, or other hydrophobic ligands. These proteins are products of a large multigene family of unlinked loci distributed throughout the genome. Each lipid-binding protein exhibits a distinctive pattern of tissue distribution. Transcriptional control, regulated by a combination of peroxisome proliferator activated receptors and CCAAT/enhancer-binding proteins, allows for a variety of both cell and tissue-specific expression patterns. In some cells, fatty acids increase the expression of the lipid-binding protein genes. Fatty acids, or their metabolites, are activators of the peroxisome proliferator–activated receptor family of transcription factors. Therefore, as the concentration of lipid in the diet increases, the expression of lipid-binding proteins coordinately increases. As revealed by X-ray crystallography, the lipid-binding proteins fold into β-barrels, forming a large internal water-filled cavity. Fatty acid ligands are bound within the cavity, occupying only about one-third of the accessible volume. The bound fatty acid is stabilized via a combination of enthalpic and entropic forces that govern ligand affinity and selectivity. Cytoplasmic lipid-binding proteins are the intracellular receptors for hydrophobic ligands, delivering them to the appropriate site for use as metabolic fuels and regulatory agents.