Pan-sulfation of bile salts markedly increases hydrophilicity and essentially abolishes self- and hetero-association with lecithin

Abstract

In chronic liver disease, partially and to a lesser extent completely (pan)-sulfated common bile salts are synthesized, yet little information is available concerning their physical-chemical characteristics. We studied solution properties of pan-sulfated common free, taurine and glycine-conjugated bile salts, and the interactions of taurodeoxycholate di-sulfate (TDC-S) with lecithin. By reverse-phase HPLC, pan-sulfated glycine and taurine-conjugated bile salts were very hydrophilic, with hydrophobic indices 1.7 to 2.5 units lower than their non-sulfated congeners. In contrast to non-sulfated species, pan-sulfated free and glycine-conjugated bile salts produced simple potentiometric titration curves without precipitation of bile salt below the p K′ A of the carboxylic acids. By quasi-elastic light scattering, critical micellar concentrations of TDC-S fell from 28 mM in 0.15 M NaCl to 3 mM in 4.0 M NaCl, a value slightly higher than that of TDC. TDC-S formed very small micelles (hydrodynamic radii approx. 11Å) that, in contrast to TDC, did not grow with increases in bile salt (7–66 mM) or NaCl (0.15–2.0 M) concentrations. TDC-S formed mixed micelles with lecithin in 0.15 M NaCl, but with a micellar zone drastically reduced compared with that of the non-sulfated congener. However, in 4 M NaCl, the micellar zone of TDC-S expanded and approached that of the non-sulfated parent compound. Therefore, under physiological conditions, pan-sulfation of common bile salts should largely eliminate their capacity to form mixed micelles with membrane lipids.