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 α-helices which are folded into a boomerang type of structure with α-helices 1, 2 and 4 in the one arm and α-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 β-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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Guidotti A, Forchetti CM, Corda MG, Konkel D, Bennett CD, Costa E: Isolation, characterization, and purification to homogeneity of an endogenous polypeptide with agonistic action on benzodiazepine receptors. Proc Natl Acad Sci USA 80: 3531–3535, 1983
Marquardt H, Todaro GJ, Shoyab M: Complete amino acid sequences of bovine and human endozepines. Homology with rat diazepam binding inhibitor. J Biol Chem 261: 9727–9731, 1986
Shoyab M, Gentry LE, Marquardt H, Todaro GJ: Isolation and characterization of a putative endogenous benzodiazepineoid (endozepine) from bovine and human brain. J Biol Chem 261: 11968–11973, 1986
Mogensen IB, Schulenberg H, Hansen HO, Spener F, Knudsen J: A novel acyl-CoA-binding protein from bovine liver. Effects on fatty acid synthesis. Biochem J 241: 189–192, 1987
Yanagibashi K, Okno Y, Kawamura M, Hall PF: The regulation of intracellular transport of cholesterol in bovine adrenal cells: Purification of a novel protein. Endocrinology 123: 2075–2082, 1988
Besman MJ, Yanagibashi K, Lee TD, Kawamura M, Hall PF, Shively JE: Identification of des-(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: Stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor. Biochemistry 86: 489–490, 1989
Chen Z-W, Agerberth B, Gell K, Andersson M, Mutt V, Östenson C-G, Efendic S, Barros-Söderling J, Persson B, Jörnvall H: Isolation and characterization of porcine diazepam-binding inhibitor, a polypeptide not only of cerebral occurrence but also common in intestinal tissues and with effects on regulation of insulin release. Eur J Biochem 174: 239–245, 1988
Andersen KV, Ludvigsen S, Mandrup S, Knudsen J, Poulsen FM: The secondary structure in solution of acyl-coenzyme A from bovine liver using1H nuclear magnetic resonance spectroscopy. Biochemistry 30: 10654–10663, 1991
Andersen KV, Poulsen FM: Refinement of the three-dimensional structure of acyl-coenzyme A binding protein using hetero-nuclear and three-dimensional nuclear magnetic resonance spectroscopy. Submitted.
Kragelund BB, Andersen KV, Madsen JC, Knudsen J, Poulsen FM: Three-dimensional structure of the complex between acylcoenzyme A binding protein and palmitoyl-coenzyme A. J Mol Biol 230, 1260–1277, 1993
Mandrup S, Hummel R, Ravn S, Jensen G, Andreasen PH, Gregersen N, Knudsen J, Kristiansen K: Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes — a typical housekeeping gene family. J Mol Biol, 228: 1011–1022, 1992
Andersen KV, Poulsen FM: The three-dimensional structure in solution of acyl-coenzyme A binding protein from bovine liver using1H nuclear magnetic resonance spectroscopy. J Mol Biol 226, 1131–1141, 1992
Mikkelsen J, Knudsen J: Acyl-CoA-binding protein from cow. Binding characteristics and cellular and tissue distribution. Biochem J 248: 709–714, 1987
Knudsen J, Højrup P, Hansen HO, Hansen HF, Roepstorff P: Acyl-CoA binding protein in the rat. Biochem J 262: 513–519, 1989
Bovolin P, Schlichting J, Miyata M, Ferrarese C, Guidotti A, Alho H: Distribution and characterization of diazepam binding inhibitor (DBI) in peripheral tissues of rat. Reg. Peptides 29: 267–281, 1990
Mocchetti I, Einstein R, Brosius J: Putative diazepam binding inhibitor peptide: cDNA clones from rat. Proc Natl Acad Sci USA 83: 7221–7225, 1986
Alho H, Harjuntausta T, Schyltz R, Pelto-Huikko M, Bovolin P: Immunohistochemistry of diazepam binding inhibitor (DBI) in the central nervous system and peripheral organs: Its possible role as an endogenous regulator of different types of benzodiazepine receptors. Neuropharmacology 30: 1381–1386, 1991
Tong Y, Rhéaume E, Simard J, Pelletier G: Localization of peripheral benzodiazepine binding sites and diazepam-binding inhibitor (DBI) mRNA in mammary glands and dimethylbenz(α)antracene (DMBA)-induced mammary tumors in the rat. Reg Peptides 33: 263–273, 1991
Alho H, Costa E, Ferrero P, Fujimoto M, Cosenza-Murphy D, Guidotti A: Diazepam-binding inhibitor: A neuropeptide located in selected neuronal populations of rat brain. Science 229: 179–182, 1985
Miyata M, Mocchetti I, Ferrarese C, Guidotti A, Costa E: Protracted treatment with diazepam increases the turnover of putative endogenous ligands for the benzodiazepine/β-carboline recognition site. Proc Natl Acad Sci USA 84: 1444–1448, 1987
Alho H, Miyata M, Korpi E, Kiianmaa K, Guidotti A: Studies of a brain polypeptide functioning as a putative endogenous ligand to benzodiazepine recognition sites in rats selectively bred for alcohol related behavior. Alcohol & Alcoholism (Suppl. 1): 637–641, 1987
Ferrarese C, Appollonio I, Frigo M, Perego M, Piolti R, Trabucchi M, Frattola L. Distribution of putative endogenous modulator of the GABAergic system in human brain. Neurology 39: 443–445, 1989
Costa E, Alho H, Santi MR, Ferrero P, Guidotti A: Cotransmission at GABAergic synapses. Prog Brain Res 68: 343–355, 1986
Ferrarese C, Vaccarino F, Alho H, Mellstrom B, Costa E, Guidotti A: Subcellular location and neuronal release of diazepam binding inhibitor. J Neurochemistry 48: 1093–1102, 1987
Tong Y, Toranzo D, Pelletier G: Localization of diazepam-binding inhibitor (DBI) mRNA in the rat brain by high resolution in situ hybridization. Neuropeptides 20: 33–40, 1991
Corda MG, Blaker WD, Mendelson WB, Guidotti A, Costa E: β-Carbolines enhance shock-induced suppression of drinking in rats. Proc natl Acad Sci USA 80: 2072–2076, 1983
Costa E, Corda MG, Guidotti A: On a brain polypeptide functioning as a putative effector for the recognition sites of benzodiazepine and betacarboline derivatives. Neuropharmacology 22: 1481–1492, 1983
Bormann J: Electrophysiological characterization of diazepam binding inhibitor (DBI) on GABAA receptors. Neuropharmacology 30: 1387–1389, 1991
Costa E, Guidotti A: Diazepam binding inhibitor (DBI): A peptide with multiple biological actions. Life Sciences 49: 325–344, 1991
Slobodyansky E, Guidotti A, Wambebe C, Berkovich A, Costa E: Isolation and characterization of a rat brain triakontatetraneuropeptide, a posttranslational product of diazepam binding inhibitor: Specific action at the RO 5-4864 recognition site. J Neurochem 15: 1276–1284, 1989
Guidotti A, Alho H, Berkovich A, Cox DH, Ferrarese C, Slobodyansky E, Santi MR, Wambebe C: DBI Process in: Allosteric modulation at different GABA/benzodiazepine receptor subtypes. In: EA Barnard and E Costa (eds) Allosteric Modulation of Amino Acid Receptors. Therapeutic Implications. Raven Press, Ltd., New York, 1989, pp 109–123
Knudsen J, Nielsen M: Diazepam-binding inhibitor: a neuropeptide and/or an acyl-CoA ester binding protein? Biochem J 265: 927–928, 1990
Anholt RRH, Pedersen PL, de Souza EB, Snyder SH: The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane. J Biol Chem 261: 576–583, 1986
Antkiewicz-Michaluk L, Guidotti A, Krueger KE: Molecular characterization and mitochondrial density of a recognition site for peripheral-type benzodiazepine ligands. Mol Pharmacol 34: 272–278, 1988
Papadopoulos V, Berkovich A, Krueger KE, Costa E, Guidotti A: Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. Endocrinology 129: 1481–1488, 1991
Hall PF: The role of diazepam binding inhibitor in the regulation of steroidogenesis. Neuropharmacology 30: 1411–1416, 1991
Papadopoulos V, Berkovich A, Krueger KE: The role of diazepam binding inhibitor and its processing products at mitochondrial benzodiazepine receptors: Regulation of steroid biosynthesis. Neuropharmacology 30: 1417–1423, 1991
Papadopoulos V, Nowzari FB, Krueger KE: Hormone-stimulated steroidogenesis is coupled to mitochondrial benzodiazepine receptors. J Biol Chem 266: 3682–3687, 1991
Brown AS, Hall PF, Shoyab M, Papadopoulos V: Mol Cell Endocrinology 83: 1–9, 1992
Massotti M, Slobodyansky E, Konkel D, Costa E, Guidotti A: Regulation of diazepam binding inhibitor in rat adrenal gland by adrenocorticotropin. Endocrinology 129: 591–596, 1991
Östenson C-G, Ahrén B, Karlsson S, Sandberg E, Efendic S: Effects of porcine diazepam-binding inhibitor on insulin and glucagon secretionin vitro from the rat endocrine pancreas. Reg Peptides 29: 143–151, 1990
Östenson C-G, Ahrén B, Johansson O, Karlsson S, Hilliges M, Efendic S: Diazepam binding inhibitor and the endocrine pancreas. Neuropharmacology 30: 1391–1398, 1991
Borboni P, Condorelli L, Stefanis PD, Sesti G, Lauro R: Modulation of insulin secretion by diazepam binding inhibitor and its processing products. Neuropharmacology 30: 1399–1403, 1991
Rosendal J, Ertbjerg P, Knudsen J: Characterization of ligand binding to acyl-CoA-binding protein. Biochem J, 290: 321–326, 1992
Rasmussen JT, Börchers T, Knudsen J: Comparison of the binding affinities of acyl-CoA-binding protein and fatty-acid-binding protein for long-chain acyl-CoA esters. Biochem J 265: 849–855, 1990
Glatz JFC, Veerkamp JH: A radiochemical procedure for the assay of fatty acid binding proteins. Analyt Biochem 132: 89–95, 1983
Ogiwara H, Tanabe T, Nikawa J, Numa S: Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A-Formation of equimolar enzyme-inhibitor complex. Eur J Biochem 89: 33–41, 1978
Woldegiorgis G, Yousufzai SYK, Shrago E: Studies on the interaction of palmitoyl coenzyme A with the adenine nucleotide translocase. J Biol Chem 257: 14783–14787, 1982
Li Q, Yamamoto N, Inoue A, Morisawa S: Fatty acyl-CoAs are potent inhibitors of the nuclear thyroid hormone receptorin vitro. J Biochem 107: 699–702, 1990
Rasmussen JT, Rosendal JR, Knudsen J: Interaction of acyl-CoA binding protein (ACBP) on processes for which acyl-CoA is a substrate, product or inhibitor. Biochem J, in press, 1993
Lust G, Lynen F: The inhibition of the fatty acid synthetase multienzyme complex of yeast by long-chain acyl-Coenzyme A compounds. Eur J Biochem 7: 68–72, 1968
Mandrup S, Jepsen R, Skøtt H, Rosendal J, Højrup P, Kristiansen K, Knudsen J: Effect of heterologous expression of acyl-CoA-binding protein (ACBP)/diazepam-binding inhibitor (DBI) on the acyl-CoA level and composition in yeast. Biochem J, 290: 369–374, 1992
Berge RK: Purification and characterization of a long-chain acyl-CoA hydrolase from rat liver microsomes. Biochim Biophys Acta 574: 321–333, 1979
Berge RK, Farstad M: Purification and characterization of longchain acyl-CoA hydrolase from rat liver mitochondria. Eur J Biochem 96: 393–401, 1979
Berge RK, Flatmark T, Osmundsen H: Enhancement of longchain acyl-CoA hydrolase activity in peroxisomes and mitochondria of rat liver by peroxisome proliferators. Eur J Biochem 141: 673–644, 1984
Mikkelsen J, Højrup P, Nielsen PF, Roepstorff P, Knudsen J: Amino acid sequence of acyl-CoA-binding protein from cow liver. Biochem J 245: 857–861, 1987
Gray PW, Glaister D, Seeburg PH, Guidotti A, Costa E: Cloning and expression of cDNA for human diazepam binding inhibitor, a natural ligand of an allosteric regulatory site of the γ-aminobutyric acid type A receptor. Proc Natl Acad Sci USA 83: 7547–7551, 1986
Owens GP, Sinha AK, Sikela JM, Hahn WE: Sequence and expression of the murine diazepam binding inhibitor. Mol Brain Res 6: 101–108, 1989
Rose TM, Schultz ER, Todaro GJ: Molecular cloning of the gene for the yeast homolog (ACB) of diazepam binding inhibitor/endozepine/acyl-CoA-binding protein. Proc Natl Acad Sci. USA 89: 11287–11291, 1992
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Knudsen, J., Mandrup, S., Rasmussen, J.T. et al. The function of acyl-CoA-binding protein (ACBP)/Diazepam binding inhibitor (DBI). Mol Cell Biochem 123, 129–138 (1993). https://doi.org/10.1007/BF01076484
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DOI: https://doi.org/10.1007/BF01076484