The fatty acid transport function of fatty acid-binding proteins.

Structural and functional features of different types of cytoplasmic fatty acid-binding proteins

Decreased hepatic triglyceride accumulation and altered fatty acid uptake in mice with deletion of the liver fatty acid-binding protein gene.

Publisher Summary This chapter provides a comprehensive overview of the current state of knowledge of the research with particular emphasis on evolving concepts of fatty acid binding proteins (FABP) structure, regulation, and function. Long-chain fatty acids provide the main energy source of most mammalian tissues and also comprise essential components of the structural lipids of cell membranes. The purification of the specific proteins responsible for the low-molecular-weight fatty-acid binding protein activity in different tissues leads to the characterization of three structurally distinct FABP of similar size, each the product of a separate gene. The three cytosolic FABP are generally named according to their tissues of greatest abundance, and comprise liver FABP, intestinal FABP, and heart muscle FABP. A role for the 40-kDa LPM-FABP as a specific cell membrane carrier in the transport of long chain fatty acids into the cells of the liver and possibly other tissues as well is available. The 14- to 15-kDa cytosolic FABPs may function as intracellular acceptors and carriers of long-chain fatty acids and their coenzyme A (CoA) esters, maintaining the ability of the tissues, particularly liver, intestine, heart, and skeletal muscle to utilize fatty acids over wide and acutely varying ranges of flux.

The cellular fatty acid binding proteins: aspects of structure, regulation, and function.

Equilibrium constants for the binding of fatty acids with fatty acid-binding proteins from adipocyte, intestine, heart, and liver measured with the fluorescent probe ADIFAB.

Fatty-acid-binding proteins (FABPs) are known as cytosolic binding sites for fatty acids and their CoA esters. Radioactively labeled and fluorescent fatty acids were used to locate and identify these proteins in bovine liver cytosol. The occurrence of two species of FABPs was demonstrated and these were designated pI6.0-FABP and pI7.0-FABP according to their isoelectric points in the delipidated state. Oleic acid/FABP binding ratios were 1 with pI6.0-FABP and 2 with pI7.0-FABP. Upon binding of oleic acid the isoelectric points of liganded FABPs shifted to pH 5.0-5.1 in each case. Both proteins were purified by removing nonbinding proteins by acid and heat denaturation and subsequent gel filtration. By making use of the pI shifts observed upon lipidation and delipidation of the binding proteins with ligand fatty acids, final purification was achieved in two fractionations by isoelectric focusing. The binding proteins (Mr 11 800 +/- 1 000) had similar amino-acid compositions (no Trp) and were not covalently modified by carbohydrate and fatty acid. Fatty acids and their CoA esters were complexed by either FABP, cholesterol only by pI-7.0-FABP, though non-stoichiometrically. 16-(9-Anthroyloxy)palmitic acid was bound by pI-7.0-FABP in a 1:1 ratio and precluded the additional binding of a straight-chain fatty acid. Electrophoretic titration curves indicated dissociation of the oleic acid/pI7.0-FABP complex below pH 5.0. It appears that fatty acids and their CoA esters are the foremost binding partners of FABPs in vivo. The results are discussed in terms of a single binding site for fatty acids per molecule FABP.

Fatty-acid-binding proteins. Occurrence of two fatty-acid-binding proteins in bovine liver cytosol and their binding of fatty acids, cholesterol, and other lipophilic ligands.

Helmut Schulenberg

Papers

Fatty-acid-binding proteins. Occurrence of two fatty-acid-binding proteins in bovine liver cytosol and their binding of fatty acids, cholesterol, and other lipophilic ligands.