Skip to main content
Log in

The function of acyl-CoA-binding protein (ACBP)/Diazepam binding inhibitor (DBI)

  • Cellular Fatty Acid-Binding Proteins II
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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

    PubMed  Google Scholar 

  2. 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

    Google Scholar 

  3. 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

    PubMed  Google Scholar 

  4. 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

    PubMed  Google Scholar 

  5. 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

    PubMed  Google Scholar 

  6. 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

    Google Scholar 

  7. 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

    PubMed  Google Scholar 

  8. 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

    PubMed  Google Scholar 

  9. 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.

  10. 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

    PubMed  Google Scholar 

  11. 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

    PubMed  Google Scholar 

  12. 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

    PubMed  Google Scholar 

  13. Mikkelsen J, Knudsen J: Acyl-CoA-binding protein from cow. Binding characteristics and cellular and tissue distribution. Biochem J 248: 709–714, 1987

    PubMed  Google Scholar 

  14. Knudsen J, Højrup P, Hansen HO, Hansen HF, Roepstorff P: Acyl-CoA binding protein in the rat. Biochem J 262: 513–519, 1989

    PubMed  Google Scholar 

  15. 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

    Google Scholar 

  16. Mocchetti I, Einstein R, Brosius J: Putative diazepam binding inhibitor peptide: cDNA clones from rat. Proc Natl Acad Sci USA 83: 7221–7225, 1986

    PubMed  Google Scholar 

  17. 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

    PubMed  Google Scholar 

  18. 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

    Google Scholar 

  19. 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

    PubMed  Google Scholar 

  20. 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

    PubMed  Google Scholar 

  21. 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

    Google Scholar 

  22. 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

    PubMed  Google Scholar 

  23. Costa E, Alho H, Santi MR, Ferrero P, Guidotti A: Cotransmission at GABAergic synapses. Prog Brain Res 68: 343–355, 1986

    PubMed  Google Scholar 

  24. 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

    Google Scholar 

  25. 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

    PubMed  Google Scholar 

  26. 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

    PubMed  Google Scholar 

  27. 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

    PubMed  Google Scholar 

  28. Bormann J: Electrophysiological characterization of diazepam binding inhibitor (DBI) on GABAA receptors. Neuropharmacology 30: 1387–1389, 1991

    PubMed  Google Scholar 

  29. Costa E, Guidotti A: Diazepam binding inhibitor (DBI): A peptide with multiple biological actions. Life Sciences 49: 325–344, 1991

    PubMed  Google Scholar 

  30. 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

    Google Scholar 

  31. 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

    Google Scholar 

  32. Knudsen J, Nielsen M: Diazepam-binding inhibitor: a neuropeptide and/or an acyl-CoA ester binding protein? Biochem J 265: 927–928, 1990

    PubMed  Google Scholar 

  33. 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

    PubMed  Google Scholar 

  34. 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

    PubMed  Google Scholar 

  35. 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

    PubMed  Google Scholar 

  36. Hall PF: The role of diazepam binding inhibitor in the regulation of steroidogenesis. Neuropharmacology 30: 1411–1416, 1991

    PubMed  Google Scholar 

  37. 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

    PubMed  Google Scholar 

  38. Papadopoulos V, Nowzari FB, Krueger KE: Hormone-stimulated steroidogenesis is coupled to mitochondrial benzodiazepine receptors. J Biol Chem 266: 3682–3687, 1991

    PubMed  Google Scholar 

  39. Brown AS, Hall PF, Shoyab M, Papadopoulos V: Mol Cell Endocrinology 83: 1–9, 1992

    Google Scholar 

  40. 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

    PubMed  Google Scholar 

  41. 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

    Google Scholar 

  42. 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

    PubMed  Google Scholar 

  43. 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

    PubMed  Google Scholar 

  44. Rosendal J, Ertbjerg P, Knudsen J: Characterization of ligand binding to acyl-CoA-binding protein. Biochem J, 290: 321–326, 1992

    Google Scholar 

  45. 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

    PubMed  Google Scholar 

  46. Glatz JFC, Veerkamp JH: A radiochemical procedure for the assay of fatty acid binding proteins. Analyt Biochem 132: 89–95, 1983

    PubMed  Google Scholar 

  47. 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

    PubMed  Google Scholar 

  48. 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

    PubMed  Google Scholar 

  49. 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

    PubMed  Google Scholar 

  50. 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

  51. 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

    PubMed  Google Scholar 

  52. 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

    Google Scholar 

  53. Berge RK: Purification and characterization of a long-chain acyl-CoA hydrolase from rat liver microsomes. Biochim Biophys Acta 574: 321–333, 1979

    PubMed  Google Scholar 

  54. Berge RK, Farstad M: Purification and characterization of longchain acyl-CoA hydrolase from rat liver mitochondria. Eur J Biochem 96: 393–401, 1979

    PubMed  Google Scholar 

  55. 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

    Google Scholar 

  56. 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

    PubMed  Google Scholar 

  57. 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

    PubMed  Google Scholar 

  58. Owens GP, Sinha AK, Sikela JM, Hahn WE: Sequence and expression of the murine diazepam binding inhibitor. Mol Brain Res 6: 101–108, 1989

    PubMed  Google Scholar 

  59. 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

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01076484

Key words

Navigation