INTRACELLULAR LIPID-BINDING PROTEINS AND THEIR GENES

Intracellular lipid-binding proteins are a family of low-molecular-wei ght 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 t he genome. Each lipid-binding protein exhibits a distinctive pattern o f tissue distribution. Transcriptional control, regulated by a combina tion of peroxisome proliferator activated receptors and CCAAT/enhancer -binding proteins, allows for a variety of both cell and tissue-specif ic expression patterns. In some cells, fatty acids increase the expres sion of the lipid-binding protein genes. Fatty acids, or their metabol ites, are activators of the peroxisome proliferator-activated receptor family of transcription factors. Therefore, as the concentration of l ipid in the diet increases, the expression of lipid-binding proteins c oordinately increases. As revealed by X-ray crystallography, the lipid -binding proteins fold into beta-barrels, forming a large internal wat er-filled cavity. Fatty acid ligands are bound within the cavity, occu pying only about one-third of the accessible volume. The bound fatty a cid is stabilized via a combination of enthalpic and entropic forces t hat govern ligand affinity and selectivity. Cytoplasmic lipid-binding proteins are the intracellular receptors for hydrophobic ligands, deli vering them to the appropriate site for use as metabolic fuels and reg ulatory agents.