Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Dec 15;320(Pt 3):729–733. doi: 10.1042/bj3200729

The binding of cholesterol and bile salts to recombinant rat liver fatty acid-binding protein.

A E Thumser 1, D C Wilton 1
PMCID: PMC1217991  PMID: 9003356

Abstract

The physiological role of liver fatty acid-binding protein (L-FABP) has yet to be clarified. An important feature of this member of the family of intracellular lipid-binding proteins is the wide range of compounds that have been identified as potential physiological ligands. By using recombinant L-FABP, the binding of cholesterol, bile salts and their derivatives has been investigated under conditions that allow a direct comparison of the binding affinities of these ligands for fatty acids. The results demonstrate an inability of L-FABP to bind cholesterol, although the anionic derivative, cholesteryl sulphate, will bind under similar assay conditions. Of the bile salts examined, lithocholate and taurolithocholate sulphate showed the greatest binding to L-FABP. It is proposed that an important function of L-FABP is to bind certain physiological amphipathic anions, thus preventing the "free' concentrations of these compounds from exceeding their critical micelle concentration, which could result in cell damage.

Full Text

The Full Text of this article is available as a PDF (232.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bass N. M. Function and regulation of hepatic and intestinal fatty acid binding proteins. Chem Phys Lipids. 1985 Aug 30;38(1-2):95–114. doi: 10.1016/0009-3084(85)90060-x. [DOI] [PubMed] [Google Scholar]
  2. Batzri S., Korn E. D. Single bilayer liposomes prepared without sonication. Biochim Biophys Acta. 1973 Apr 16;298(4):1015–1019. doi: 10.1016/0005-2736(73)90408-2. [DOI] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Burrier R. E., Manson C. R., Brecher P. Binding of acyl-CoA to liver fatty acid binding protein: effect on acyl-CoA synthesis. Biochim Biophys Acta. 1987 Jun 23;919(3):221–230. doi: 10.1016/0005-2760(87)90261-x. [DOI] [PubMed] [Google Scholar]
  5. Dawson P. A., Oelkers P. Bile acid transporters. Curr Opin Lipidol. 1995 Apr;6(2):109–114. doi: 10.1097/00041433-199504000-00009. [DOI] [PubMed] [Google Scholar]
  6. Dempsey M. E. Regulation of lipid metabolism by a lipid-carrying protein. Curr Top Cell Regul. 1984;24:63–86. doi: 10.1016/b978-0-12-152824-9.50014-9. [DOI] [PubMed] [Google Scholar]
  7. Dietrich A., Dieminger W., Fuchte K., Stoll G. H., Schlitz E., Gerok W., Kurz G. Functional significance of interaction of H-FABP with sulfated and nonsulfated taurine-conjugated bile salts in rat liver. J Lipid Res. 1995 Aug;36(8):1745–1755. [PubMed] [Google Scholar]
  8. Glatz J. F., Veerkamp J. H. A radiochemical procedure for the assay of fatty acid binding by proteins. Anal Biochem. 1983 Jul 1;132(1):89–95. doi: 10.1016/0003-2697(83)90429-3. [DOI] [PubMed] [Google Scholar]
  9. Haunerland N., Jagschies G., Schulenberg H., Spener F. 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. Hoppe Seylers Z Physiol Chem. 1984 Mar;365(3):365–376. doi: 10.1515/bchm2.1984.365.1.365. [DOI] [PubMed] [Google Scholar]
  10. Jakoby M. G., Miller K. R., Toner J. J., Bauman A., Cheng L., Li E., Cistola D. P. Ligand-protein electrostatic interactions govern the specificity of retinol- and fatty acid-binding proteins. Biochemistry. 1993 Jan 26;32(3):872–878. doi: 10.1021/bi00054a019. [DOI] [PubMed] [Google Scholar]
  11. Kaikaus R. M., Bass N. M., Ockner R. K. Functions of fatty acid binding proteins. Experientia. 1990 Jun 15;46(6):617–630. doi: 10.1007/BF01939701. [DOI] [PubMed] [Google Scholar]
  12. Ketterer B., Tipping E., Hackney J. F., Beale D. A low-molecular-weight protein from rat liver that resembles ligandin in its binding properties. Biochem J. 1976 Jun 1;155(3):511–521. doi: 10.1042/bj1550511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kim H. K., Storch J. Free fatty acid transfer from rat liver fatty acid-binding protein to phospholipid vesicles. Effect of ligand and solution properties. J Biol Chem. 1992 Jan 5;267(1):77–82. [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Liscum L., Dahl N. K. Intracellular cholesterol transport. J Lipid Res. 1992 Sep;33(9):1239–1254. [PubMed] [Google Scholar]
  16. Miller K. R., Cistola D. P. Titration calorimetry as a binding assay for lipid-binding proteins. Mol Cell Biochem. 1993 Jun 9;123(1-2):29–37. doi: 10.1007/BF01076472. [DOI] [PubMed] [Google Scholar]
  17. Nemecz G., Schroeder F. Selective binding of cholesterol by recombinant fatty acid binding proteins. J Biol Chem. 1991 Sep 15;266(26):17180–17186. [PubMed] [Google Scholar]
  18. Rolf B., Oudenampsen-Krüger E., Börchers T., Faergeman N. J., Knudsen J., Lezius A., Spener F. Analysis of the ligand binding properties of recombinant bovine liver-type fatty acid binding protein. Biochim Biophys Acta. 1995 Dec 7;1259(3):245–253. doi: 10.1016/0005-2760(95)00170-0. [DOI] [PubMed] [Google Scholar]
  19. Russell D. W., Setchell K. D. Bile acid biosynthesis. Biochemistry. 1992 May 26;31(20):4737–4749. doi: 10.1021/bi00135a001. [DOI] [PubMed] [Google Scholar]
  20. Rüstow B., Risse S., Kunze D. Endogenes Lipidmuster, Organverteilung und Diätbeeinflussung einer fettsäurebindenden Proteinfraktion des Leberzytosols der Ratte. Acta Biol Med Ger. 1982;41(5):439–445. [PubMed] [Google Scholar]
  21. Scallen T. J., Pastuszyn A., Noland B. J., Chanderbhan R., Kharroubi A., Vahouny G. V. Sterol carrier and lipid transfer proteins. Chem Phys Lipids. 1985 Sep;38(3):239–261. doi: 10.1016/0009-3084(85)90019-2. [DOI] [PubMed] [Google Scholar]
  22. Schroeder F., Dempsey M. E., Fischer R. T. Sterol and squalene carrier protein interactions with fluorescent delta 5,7,9(11)-cholestatrien-3 beta-ol. J Biol Chem. 1985 Mar 10;260(5):2904–2911. [PubMed] [Google Scholar]
  23. Sorof S. Modulation of mitogenesis by liver fatty acid binding protein. Cancer Metastasis Rev. 1994 Dec;13(3-4):317–336. doi: 10.1007/BF00666102. [DOI] [PubMed] [Google Scholar]
  24. Stolz A., Takikawa H., Ookhtens M., Kaplowitz N. The role of cytoplasmic proteins in hepatic bile acid transport. Annu Rev Physiol. 1989;51:161–176. doi: 10.1146/annurev.ph.51.030189.001113. [DOI] [PubMed] [Google Scholar]
  25. Storch J., Bass N. M. Transfer of fluorescent fatty acids from liver and heart fatty acid-binding proteins to model membranes. J Biol Chem. 1990 May 15;265(14):7827–7831. [PubMed] [Google Scholar]
  26. Takikawa H., Kaplowitz N. Binding of bile acids, oleic acid, and organic anions by rat and human hepatic Z protein. Arch Biochem Biophys. 1986 Nov 15;251(1):385–392. doi: 10.1016/0003-9861(86)90086-x. [DOI] [PubMed] [Google Scholar]
  27. Thumser A. E., Evans C., Worrall A. F., Wilton D. C. Effect on ligand binding of arginine mutations in recombinant rat liver fatty acid-binding protein. Biochem J. 1994 Jan 1;297(Pt 1):103–107. doi: 10.1042/bj2970103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Thumser A. E., Voysey J. E., Wilton D. C. The binding of lysophospholipids to rat liver fatty acid-binding protein and albumin. Biochem J. 1994 Aug 1;301(Pt 3):801–806. doi: 10.1042/bj3010801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thumser A. E., Voysey J., Wilton D. C. Mutations of recombinant rat liver fatty acid-binding protein at residues 102 and 122 alter its structural integrity and affinity for physiological ligands. Biochem J. 1996 Mar 15;314(Pt 3):943–949. doi: 10.1042/bj3140943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thumser A. E., Wilton D. C. Characterization of binding and structural properties of rat liver fatty-acid-binding protein using tryptophan mutants. Biochem J. 1994 Jun 15;300(Pt 3):827–833. doi: 10.1042/bj3000827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thumser A. E., Wilton D. C. The binding of natural and fluorescent lysophospholipids to wild-type and mutant rat liver fatty acid-binding protein and albumin. Biochem J. 1995 Apr 1;307(Pt 1):305–311. doi: 10.1042/bj3070305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Veerkamp J. H., Maatman R. G. Cytoplasmic fatty acid-binding proteins: their structure and genes. Prog Lipid Res. 1995;34(1):17–52. doi: 10.1016/0163-7827(94)00005-7. [DOI] [PubMed] [Google Scholar]
  33. Vincent S. H., Muller-Eberhard U. A protein of the Z class of liver cytosolic proteins in the rat that preferentially binds heme. J Biol Chem. 1985 Nov 25;260(27):14521–14528. [PubMed] [Google Scholar]
  34. Wilkinson T. C., Wilton D. C. Studies on fatty acid-binding proteins. The detection and quantification of the protein from rat liver by using a fluorescent fatty acid analogue. Biochem J. 1986 Sep 1;238(2):419–424. doi: 10.1042/bj2380419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wilson M. D., Rudel L. L. Review of cholesterol absorption with emphasis on dietary and biliary cholesterol. J Lipid Res. 1994 Jun;35(6):943–955. [PubMed] [Google Scholar]
  36. Wilton D. C. Studies on fatty-acid-binding proteins. The purification of rat liver fatty-acid-binding protein and the role of cysteine-69 in fatty acid binding. Biochem J. 1989 Jul 1;261(1):273–276. doi: 10.1042/bj2610273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Worrall A. F., Evans C., Wilton D. C. Synthesis of a gene for rat liver fatty-acid-binding protein and its expression in Escherichia coli. Biochem J. 1991 Sep 1;278(Pt 2):365–368. doi: 10.1042/bj2780365. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES