Journal of Lipid Research, Vol 25, 1263-1271, Copyright © 1984 by Lipid Research, Inc.
Critical evaluation of the existence of so-called tissue-bound lithocholate in human liver tissue by selected ion monitoring
J Yanagisawa, Y Akashi, H Miyazaki and F Nakayama
Monohydroxy bile acids in liver tissue may be of importance because of
their hepatotoxicity and strong cholestatic effects. Recently, the
existence of lithocholate in liver tissue in two forms was suggested by
Nair et al. (Lipids. 1977. 12: 922-929) i.e., either in free form or as
so-called tissue-bound lithocholate released exclusively by cholylglycine
hydrolase treatment. The presence of the latter aroused much interest in
relation to its hepatotoxicity and possible role in tumor induction. In the
present investigation lithocholyl-epsilon-L- lysine, proposed as the
predominant tissue-bound bile acid, was synthesized and its metabolic
behavior was tested. Lithocholyl-epsilon- lysine was not deconjugated by
cholylglycine hydrolase treatment but only by alkaline hydrolysis. Bile
acids in seven cirrhotic and three noncirrhotic liver samples were
extracted with 95% ethanol-0.1% ammonium hydroxide. The bile acids in the
extract and residue were quantified by glass capillary gas-liquid
chromatography using selected ion monitoring. The presence of so-called
tissue-bound lithocholate could not be substantiated in either cirrhotic or
noncirrhotic liver tissues. Nearly complete extraction of lithocholate was
achieved by the use of organic solvent alone. Therefore, tissue-bound
lithocholate, if it exists at all, may be attached to tissue by a physical
linkage which can be disrupted by the use of conventional organic solvent.
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