Journal of Lipid Research, Vol 37, 1045-1056, Copyright © 1996 by Lipid Research, Inc.
3 alpha, 7 alpha, 12 alpha-trihydroxy-24-nor-5 beta-cholan-23- sulfonate: synthesis and suitability for the study of cholate transport
D Schwab, H Thom, J Heinze and G Kurz
Institut fur Organische Chemie und Biochemie, Universitat Freiburg, Germany.
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.
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