The function of acyl-CoA-binding protein (ACBP)/Diazepam binding inhibitor (DBI) |
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Authors: | Jens Knudsen Susanne Mandrup Jan Trige Rasmussen Per Hove Andreasen Flemming Poulsen Karsten Kristiansen |
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Institution: | (1) Institute of Biochemistry, Odense University, Campusvej 55, DK-5230 Odense, Denmark;(2) Department of Chemistry, Carlsberg Laboratory, Gamle Carlsbergvej 10, DK-2500 Copenhagen Valby, Denmark;(3) Department of Molecular Biology, Odense University, Campusvej 55, DK-5230 Odense M, Denmark |
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Abstract: | Acyl-CoA-binding protein has been isolated independently by five different groups based on its ability to (1) displace diazepam from the GABAA receptor, (2) affect cell growth, (3) induce medium-chain acyl-CoA-ester synthesis, (4) stimulate steroid hormone synthesis, and (5) affect glucose-induced insulin secretion. In this survey evidence is presented to show that ACBP is able to act as an intracellular acyl-CoA transporter and acyl-CoA pool former. The rat ACBP genomic gene consists of 4 exons and is actively expressed in all tissues tested with highest concentration being found in liver. ACBP consists of 86 amino acid residues and contains 4 -helices which are folded into a boomerang type of structure with -helices 1, 2 and 4 in the one arm and -helix 3 and an open loop in the other arm of the boomerang. ACBP is able to stimulate mitochondrial acyl-CoA synthetase by removing acyl-CoA esters from the enzyme. ACBP is also able to desorb acyl-CoA esters from immobilized membranes and transport and deliver these for mitochondrial -oxidation. ACBP efficiently protects acetyl-CoA carboxylase and the mitochondrial ADP/ATP translocase against acyl-CoA inhibition. Finally, ACBP is shown to be able to act as an intracellular acyl-CoA pool former by overexpression in yeast. The possible role of ACBP in lipid metabolism is discussed. |
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Keywords: | acyl-CoA-binding protein acyl-CoA transport and pool formation diazepam-binding-inhibitor heterologous expression in yeast primary and tertiary structure tissue distribution |
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