3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-cholan-23-sulfonate: synthesis and suitability for the study of cholate transport.
In order to facilitate the study of transport processes of unconjugated C-24 bile salts, simple syntheses of 3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-cholan-23-sulfonate (norcholansulfonate) and 3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-[7 beta 5H] cholan-23-sulfonate were devised. The hydrophilic-hydrophobic properties of norcholansulfonate, as determined by its chromatographic behavior as well as by its partition between l-octanol and water, are more similar to those of cholyltaurine than to those of cholate. Self-association of norcholansulfonate in phosphate buffer, pH 7.4, with an ionic strength of 150 mM begins at a concentration of about 1 mM, comparable to that of cholyltaurine and cholate, as determined by spectral changes in fluorescence emissions of {N-[7-(4-nitrobenzo-2-oxa-1, 3-diazol)]-7b-amino-3a, 12a-dihydroxy-5b-cholan-24 - oyl}-2'-aminoethanesulfonate (7 beta-NBD-NCT). The apparent CMC value obtained from solubilization of the dye Orange OT, 8.5 mM, is comparable to that of cholytaurine. 7.5 mM, and lower than that of cholate, 9.5 mM. Norcholansulfonate is readily taken up by rat liver and completely excreted unmetabolized into bile with about the same secretion maximum (Tm) as cholyltaurine. Biliary excretion of norcholansulfonate is inhibited by cholyltaurine, and, vice versa, norcholansulfonate inhibits cholyltaurine secretion. Concerning metabolism and excretion, norcholansulfonate with the sulfonate group in the position where cholate has the carboxylate group should behave as an appropriate cholate analogue in mediated transport processes.
Schwab
D
D
Institut für Organische Chemie und Biochemie, Universität Freiburg, Germany.
Thom
H
H
Heinze
J
J
Kurz
G
G
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002264:Carboxylic Acids / Q000737:chemistry; D002757:Cholanes / Q000138:chemical synthesis* / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013451:Sulfonic Acids / Q000737:chemistry; D014867:Water / Q000737:chemistry
C102743:3,7,12-trihydroxy-24-norcholan-23-sulfonate; D002264:Carboxylic Acids; D002757:Cholanes; D002793:Cholic Acids; D013451:Sulfonic Acids; D014867:Water; D019826:Cholic Acid