Interactions of unconjugated bilirubin with vesicles, cyclodextrins and micelles: New modeling and the role of high pKa values
Tóm tắt
Unconjugated bilirubin (UCB) is an unstable substance with very low aqueous solubility. Its aqueous pKa values affect many of its interactions, particularly their pH-dependence. A companion paper shows that only our prior solvent partition studies, leading to pKa values of 8.12 and 8.44, met all essential requirements for valid pKa determinations. Other published values, generally lower, some below 5.0, were shown to be invalid. The present work was designed to derive suitable models for interpreting published data on the pH-dependent binding of UCB with four agents, mentioned below, chosen because they are not, themselves, sensitive to changes in the pH range 4-10, and the data, mainly spectrometric, were of reasonable quality. These analyses indicated that the high pKa values, dianion dimerization constant and solubilities of UCB at various pH values, derived from our partition studies, along with literature-derived pH- and time-dependent supersaturation effects, were essential for constructing useful models that showed good qualitative, and sometimes quantitative, fits with the data. In contrast, published pKa values below 5.0 were highly incompatible with the data for all systems considered. The primary species of bound UCB in our models were: undissociated diacid for phosphatidylcholine, dianion for dodecyl maltoside micelles and cyclodextrins, and both monoanions and dianion for sodium taurocholate. The resulting binding versus pH profiles differed strikingly from each other. The insights derived from these analyses should be helpful to explore and interpret UCB binding to more complex, pH-sensitive, physiological moieties, such as proteins or membranes, in order to understand its functions.
Tài liệu tham khảo
Ostrow JD, Mukerjee P, Tiribelli C: Structure and binding of unconjugated bilirubin: relevance for physiological and pathophysiological function. J Lipid Res. 1994, 35: 1715-1737.
Mukerjee P, Ostrow JD: Review: Bilirubin pKa studies: new models and theories indicate high pKa values in water, dimethylformamide and DMSO. BMC Biochemistry. 2010, 11: 15-
Boiadjiev SE, Watters K, Wolf S, Lai BN, Welch WH, McDonagh AF, Lightner DA: pKa and aggregation of bilirubin: titrimetric and ultracentrifugation studies on water-soluble pegylated conjugates of bilirubin and fatty acids. Biochemistry. 2004, 43: 15617-15632. 10.1021/bi0481491.
Hahm JS, Ostrow JD, Mukerjee P, Celic L: Ionization and self-association of unconjugated bilirubin, determined by rapid solvent partition from chloroform, with further studies of bilirubin solubility. J Lipid Res. 1992, 33: 1123-1137.
Ostrow JD, Mukerjee P: Revalidation and rationale for high pKa values of unconjugated bilirubin. BMC Biochem. 2007, 8: 7-10.1186/1471-2091-8-7.
Mukerjee P, Ostrow JD, Tiribelli C: Low solubility of unconjugated bilirubin in dimethylsulfoxide - water systems: implications for pK a determinations. BMC Biochemistry. 2002, 3: 17-10.1186/1471-2091-3-17.
Brodersen R, Theilgaard J: Bilirubin colloid formation in neutral aqueous solution. Scand J Clin Lab Invest. 1969, 24: 395-398. 10.3109/00365516909080178.
Wosiewitz U, Schroebler S: Solubilization of unconjugated bilirubin by bile salts. Experientia. 1979, 35: 717-718. 10.1007/BF01968199.
Ostrow JD, Celic L, Mukerjee P: Molecular and micellar associations in the pH-dependent stable and metastable dissolution of unconjugated bilirubin by bile salts. J Lipid Res. 1988, 29: 335-348.
With TK: Biology of Bile Pigments. 1954, Copenhagen: Arne Frost-Hansen
With TK: Bile Pigments: Chemical, Biological and Clinical Aspects. 1968, New York: Academic Press
Tipping E, Ketterer B, Christodoulides L: Binding to egg phosphatidylcholine of some organic anions (bromsulphophthalein, oestrone sulphate, haem and bilirubin) that bind to ligandin and aminoazo-dye binding protein A. Biochem J. 1979, 180: 327-337.
Kano K, Ishimura T: Properties of alkyl β-D-glucoside and alkyl β-D-maltoside micelles. J Chem Soc Perkin Trans II. 1995, 1655-1660. 10.1039/p29950001655.
Kano K, Arimoto S, Ishimura T: Conformational enantiomerism of bilirubin and pamoic acid induced by protonated aminocyclodextrins. J Chem Soc Perkin Trans II. 1995, 1661-1667. 10.1039/p29950001661.
D'Alagni M, Galantini L, Giglio E, Gavuzzo E, Scaramuzza L: Micellar aggregates of sodium glycocholate and sodium taurocholate and their interaction complexes with bilirubin-IXα. J Chem Soc Faraday Trans. 1994, 90: 1523-1532. 10.1039/ft9949001523.
Eriksen EF, Danielsen H, Brodersen R: Bilirubin-liposome interaction. Binding of bilirubin dianion, protonization and aggregation of bilirubin acid. J Biol Chem. 1981, 256: 4269-4274.
Lightner DA, Holmes DL, McDonagh AF: Dissociation constants of water-insoluble carboxylic acids by 13C-NMR. p Kas of mesobiliverdin-XIIIα and mesobilirubin-XIIIα. Experientia. 1996, 51: 639-642. 10.1007/BF01969747.
Holmes DL, Lightner DA: Synthesis and acidity constants of 13CO2H-labelled dicarboxylic acids. p Kas from 13C-NMR. Tetrahedron. 1996, 52: 5319-5338. 10.1016/0040-4020(96)00153-6.
Lightner DA, Holmes DL, McDonagh AF: On the acid dissociation constants of bilirubin and biliverdin. pKavalues from 13C NMR spectroscopy. J Biol Chem. 1996, 271: 2397-2405. 10.1074/jbc.271.5.2397.
McDonagh AF, Phimster A, Boiadjiev SE, Lightner DA: Dissociation constants of carboxylic acids by 13C-NMR in DMSO/water. Tetrahedron Letters. 1999, 40: 8515-8518. 10.1016/S0040-4039(99)01841-9.
Hahm JS, Mun GH, Lee HL, Eun CS, Park JY, Han DS, Choi HS, Ahn YH: [Interactions of unconjugated bilirubin with bile acid by rapid solvent partition]. Taehan Kan Hakhoe Chi. 2002, 8: 80-89.
Cestaro B, Cervato G, Ferrari S, Di Silvestro G, Monti D, Manitto P: Interaction of bilirubin with small unilamellar vesicles of dipalmitoylphosphatidylcholine. Ital J Biochem. 1983, 32: 318-329.
Garvin JE, Karnovsky ML: The titration of some phosphatides and related compounds in a non-aqueous system. J Biol Chem. 1956, 221: 211-222.
Jukes TH: The electrometric titration of lecithin and cephalin. J Biol Chem. 1934, 107: 783-787.
Carey MC, Spivak W: Physical chemistry of bile pigments and porphyrins with particular reference to bile. Bile Pigments and Jaundice; Molecular, Metabolic and Medical Aspects. Edited by: Ostrow JD. 1986, New York: Marcel Dekker, 81-132.
Zucker SD, Gössling W: Mechanism of hepatocellular uptake of albumin-bound bilirubin. Biochim Biophys Acta. 2000, 1463: 197-208. 10.1016/S0005-2736(99)00196-0.
Zucker SD, Gössling W, Bootle EJ, Sterritt C: Localization of bilirubin in phospholipid bilayers by parallax analysis of fluorescence quenching. J Lipid Res. 2001, 42: 1377-1388.
Vazquez J, Garcia-Calvo M, Valdivieso F, Mayer F, Mayer FJ: Interaction of bilirubin with the synaptosomal plasma membrane. J Biol Chem. 1988, 263: 1255-1265.
Zucker SD, Storch J, Zeidel ML, Gollan JL: Mechanism of the spontaneous transfer of unconjugated bilirubin between small unilamellar phosphatidylcholine vesicles. Biochemistry. 1992, 31: 3184-3192. 10.1021/bi00127a020.
Vazquez J, Ortega G, Valdivieso F, Mayor F: Interaction of bilirubin with gangliosides. J Biochem (Tokyo). 1989, 106: 139-142.
Amit Y, Fedunec S, Thomas PD, Poznansky MJ, Schiff D: Bilirubin-neural cell interaction: characterization of initial cell surface binding leading to toxicity in the neuroblastoma cell line N-115. Biochim Biophys Acta. 1990, 1055: 36-42. 10.1016/0167-4889(90)90088-U.
Rashid H, Ali MK, Tayyab S: Effect of pH and temperature on the binding of bilirubin to human erythrocyte membranes. J Biosci. 2000, 25: 157-161.
Sato H, Kashiwamata S: Interaction of bilirubin with human erythrocyte membranes. Biochem J. 1983, 210: 489-496.
Bratlid D: The effect of pH on bilirubin binding by human erythrocytes. Scand J Clin Lab Invest. 1972, 29: 453-459. 10.3109/00365517209080265.
Wennberg RP: The importance of free bilirubin acid salt in bilirubin uptake by erythrocytes and mitochondria. Pediatr Res. 1988, 23: 443-447. 10.1203/00006450-198804000-00021.
Lightner DA, Gawronski JK, Gawronska K: Conformational enantiomerism in bilirubin. Selection by cyclodextrins. J Am Chem Soc. 1985, 107: 2456-2461. 10.1021/ja00294a042.
Carey MC: Bile acids and bile salts: ionization and solubility properties. Hepatology. 1984, 4: 66S-71S. 10.1002/hep.1840040812.
Kano K, Tsujino N, Kim M: Mechanisms for steroid-induced conformational enantio-merism of bilirubin in protic solvents. J Chem Soc Perkin Trans II. 1992, 1747-1752. 10.1039/p29920001747.
Harman AD, Kibbey RG, Sablik MA, Fintschenko Y, Kurtin WE, Bushey MM: Micellar electrokinetic capillary chromatography analysis of the behavior of bilirubin in micellar solutions. J Chromatogr A. 1993, 652: 525-533. 10.1016/0021-9673(93)83274-V.
Kurtin WE, Enz J, Dunsmoor C, Evans N, Lightner DA: Acid dissociation constants of bilirubin and related carboxylic acid compounds in bile salt solutions. Arch Biochem Biophys. 2000, 381: 83-91. 10.1006/abbi.2000.1949.
D'Alagni M, Delfini M, Galantini L, Giglio E: A study of the interaction of bilirubin with sodium deoxycholate in aqueous solutions. J Phys Chem. 1992, 96: 10520-10528. 10.1021/j100204a073.
D'Alagni M, D'Archivio AA, Giglio E, Scaramuzza L: Structure of sodium and rubidium taurodeoxycholate micellar aggregates and their interaction complexes with bilirubin-IXα. J Phys Chem. 1994, 98: 343-353. 10.1021/j100052a056.
Brodersen R: Prevention of kernicterus, based on recent progress in bilirubin chemistry. Acta Paediatr Scand. 1977, 66: 625-634. 10.1111/j.1651-2227.1977.tb07959.x.
Brodersen R: Binding of bilirubin to albumin; implications for prevention of bilirubin encephalopathy in the newborn. CRC Crit Rev Clin Lab Sci. 1979, 11: 305-399.
Brodersen R: Physical chemistry of bilirubin: Binding to macromolecules and membranes. Bilirubin. Chemistry. Edited by: Heirwegh KPM, Brown SB. 1982, Boca Raton, FL: CRC Press, 1: 75-123.
Brodersen R: Aqueous solubility, albumin binding and tissue distribution of bilirubin. Bile Pigments and Jaundice; Molecular, Metabolic and Medical Aspects. Edited by: Ostrow JD. 1986, New York: Marcel Dekker, 157-181.
Brodersen R, Stern L: Deposition of bilirubin acid in the central nervous system - A hypothesis for the development of kernicterus. Acta Paediatr Scand. 1990, 79: 12-19. 10.1111/j.1651-2227.1990.tb11323.x.
Ostrow JD, Pascolo L, Shapiro SM, Tiribelli C: New concepts in bilirubin encephalopathy. Eur J Clin Invest. 2003, 33: 988-997. 10.1046/j.1365-2362.2003.01261.x.
Ostrow JD, Pascolo L, Brites D, Tiribelli C: Molecular basis of bilirubin-induced neurotoxicity. Trends Mol Med. 2004, 10: 65-70. 10.1016/j.molmed.2003.12.003.