ACYL-COA-BINDING PROTEINS - MULTIPLICITY AND FUNCTION

The physiological role of long-chain fatty acyl-CoA is thought to be p rimarily in intermediary metabolism of fatty acids. However, recent da ta show that nM to mu M levels of these lipophilic molecules are poten t regulators of cell functions in vitro. Although long-chain fatty acy l-CoA are present at several hundred mu M concentration in the cell, v ery little long-chain fatty acyl-CoA actually exists as free or unboun d molecules, but rather is bound with high affinity to membrane lipids and/or proteins. Recently, there is growing awareness that cytosol co ntains nonenzymatic proteins also capable of binding long-chain fatty acyl-CoA with high affinity. Although the identity the cytosolic long- chain fatty acyl-CoA binding protein(s) has been the subject of some c ontroversy, there is growing evidence that several diverse nonenzymati c cytosolic proteins will bind long-chain fatty acyl-CoA. Not only doe s acyl-CoA binding protein specifically bind medium and long-chain fat ty acyl-CoA (LCFA-CoA), but ubiquitous proteins with multiple ligand s pecificities such as the fatty acid binding proteins and sterol carrie r protein-2 also bind LCFA-CoA with high affinity. The potential of th ese acyl-CoA binding proteins to influence the level of free LCFA-CoA and thereby the amount of LCFA-CoA bound to regulatory sites in protei ns and enzymes is only now being examined in detail. The purpose of th is article is to explore the identity, nature, function, and pathobiol ogy of these fascinating newly dis covered long-chain fatty acyl-CoA b inding proteins. The relative contributions of these three different p rotein families to LCFA-CoA utilization and/or regulation of cellular activities are the focus of new directions in this field.