Abstract
Cholesterol (C) needed for bile acid synthesis is recruited from de novo synthesized C as well as lipoprotein C. It is not known whether C used for the primary bile acids and biliary C originates from one or more hepatic C-pools. By using different C vehicles, i.e. lipoproteins and liposomes, we tried to discriminate between metabolic pathways for the formation of bile acids in the liver. Studies were undertaken in rats with a permanent biliary drainage. Bile acids were analyzed by HPLC and capillary GC. (3H−)C was administered intravenously in three vehicles: lipoproteins (LP), multilamellar vesicles (MLV) and small unilamellar vesicles (SUV). For all vehicles over 75% of C was excreted in bile as bile acids after 120 hrs. Initial biliary excretion was highest for LP (5.7% at 1 h after injection), followed by MLV and SUV (1.3 and 0.9% resp.). No differences were detectable between the specific activities of the excreted bile acids 12 h after injection, but at lh the specific activity of murocholic acids was markedly increased in experiments with SUV-C, but not with LMV- or LP-2. Also the gly/tau conjugation ratio was increased for SUV-C at 1 h.
We conclude that more than one C pool in the hepatocytes exists from which C is recruited for bile acid synthesis, with SUV-C preferentially used for muricholic acids synthesis. Zonal heterogeneity might be responsible for the observed differences.
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Spanjer, H., Kuipers, F., Havinga, R. et al. PREFERENTIAL USE OF LIPOSOMAL-CHOLESTEROL FOR THE FORMATION OF MURICHOLIC ACID IN THE RAT. Pediatr Res 19, 1074 (1985). https://doi.org/10.1203/00006450-198510000-00036
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DOI: https://doi.org/10.1203/00006450-198510000-00036