This paper describes the derivation of a bile salt monomeric hydrophobicity index that quantitatively defines the composite hydrophilic-hydrophobic balance of a mixture of bile salts. The index is based on the logarithms of bile salt capacity factors determined using reversed phase high performance liquid chromatography (HPLC) (stationary phase octadecyl silane; mobile phase methanol-water 70:30 w/w, ionic strength 0.15). It has been standardized arbitrarily to set indices of taurocholate and taurolithocholate to 0 and 1, respectively. Indices of tauroursodeoxycholate, taurohyodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate were found to be -0.47, -0.35, +0.46, and +0.59, respectively. Whereas capacity factors and hydrophobicity indices of taurine-conjugated bile salts were constant for pH 2.8-9.0, the hydrophilic-hydrophobic balance of glycine-conjugated and unconjugated bile salts was strongly influenced by pH. At alkaline pH (greater than 8.5), hydrophobicity indices of fully ionized unconjugated (n = 4) and glycine-conjugated (n = 6) bile salts differed by only 0.14 +/- 0.02 and 0.05 +/- 0.01, respectively, from those of the corresponding taurine conjugates. At acid pH (less than 3.5) the hydrophobicity indices of four unconjugated bile acids (protonated form) exceeded those of the corresponding salts (ionized form) by 0.76 +/- 0.04; indices of six glycine-conjugated bile acids exceeded those of the corresponding salts by only 0.26 +/- 0.03. Capacity factors of the salt forms of cholate and its conjugates increased dramatically with increasing ionic strength of the mobile phase; retention of the protonated forms (cholic and glycocholic acids) was only minimally influenced by ionic strength. Thus the difference in hydrophilic-hydrophobic balance between a bile acid and its corresponding salt decreases with increasing ionic strength. Examples are given of calculation of hydrophobicity indices for biliary bile salts (fully ionized) from four species under conditions of intact enterohepatic circulation. Mean values, from least to most hydrophobic, were: rat (-0.31) less than dog (0.11) less than hamster (0.22) less than human (0.32). This study provides a rational basis for calculating the hydrophilic-hydrophobic balance of mixed bile salt solutions over a broad range of pH.
Molina LM, Zhu J, Li Q, Pradhan-Sundd T, Krutsenko Y, Sayed K, Jenkins N, Vats R, Bhushan B, Ko S, Hu S, Poddar M, Singh S, Tao J, Sundd P, Singhi A, Watkins S, Ma X, Benos PV, Feranchak A, Michalopoulos G, Nejak-Bowen K, Watson A, Bell A, Monga SP.
Cell Rep. 2021 Jul 06;36(1):109310. doi: 10.1016/j.celrep.2021.109310.
PMID: 34233187
Hutka B, Lázár B, Tóth AS, Ágg B, László SB, Makra N, Ligeti B, Scheich B, Király K, Al-Khrasani M, Szabó D, Ferdinandy P, Gyires K, Zádori ZS.
Front Pharmacol. 2021 Jun 04;12:664177. doi: 10.3389/fphar.2021.664177. eCollection 2021.
PMID: 34149417
Zhao X, Setchell KDR, Huang R, Mallawaarachchi I, Ehsan L, Dobrzykowski Iii E, Zhao J, Syed S, Ma JZ, Iqbal NT, Iqbal J, Sadiq K, Ahmed S, Haberman Y, Denson LA, Ali SA, Moore SR.
J Nutr. 2021 Dec 03;151(12):3689-3700. doi: 10.1093/jn/nxab321.
PMID: 34718665
de Boer JF, de Vries HD, Palmiotti A, Li R, Doestzada M, Hoogerland JA, Fu J, La Rose AM, Westerterp M, Mulder NL, Hovingh MV, Koehorst M, Kloosterhuis NJ, Wolters JC, Bloks VW, Haas JT, Dombrowicz D, Staels B, van de Sluis B, Kuipers F.
Cell Mol Gastroenterol Hepatol. 2021;11(4):1045-1069. doi: 10.1016/j.jcmgh.2020.12.004. Epub 2020 Dec 10.
PMID: 33309945
Molina LM, Zhu J, Li Q, Pradhan-Sundd T, Krutsenko Y, Sayed K, Jenkins N, Vats R, Bhushan B, Ko S, Hu S, Poddar M, Singh S, Tao J, Sundd P, Singhi A, Watkins S, Ma X, Benos PV, Feranchak A, Michalopoulos G, Nejak-Bowen K, Watson A, Bell A, Monga SP.
Cell Rep. 2021 Jul 06;36(1):109310. doi: 10.1016/j.celrep.2021.109310.
PMID: 34233187
