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Biosynthesis of cholestanol from bile acid intermediates in the rabbit and the rat.

Abstract
Biliary 7 alpha-hydroxy-4-cholesten-3-one (an intermediate in bile acid biosynthesis) may be 7 alpha-dehydroxylated in the gut and further metabolized to cholestanol (Skrede, S., and Björkhem, I. (1982) J. Biol. Chem. 257, 8363-8367). We have now evaluated the quantitative importance of pathway(s) to cholestanol with 7 alpha-hydroxylated C27 steroids as intermediates. After feeding conventionally fed rabbits or rats or germ-free rats with [7 alpha-3H]cholesterol and [4-14C]cholesterol, tissue cholestanol could be isolated with about a 20% lower 3H/14C ratio than present in cholesterol. We conclude that there is a pathway to cholestanol involving 7 alpha-hydroxylated intermediates. Intestinal microorganisms are not essential for this pathway, which accounts for at most 20% of the cholestanol formed in these species. In bile fistula rats, there was also a significant conversion of intraperitoneally injected [7 beta-3H]7 alpha-hydroxycholesterol and [4-14C]7 alpha-hydroxy-4-cholesten-3-one into cholestanol. The enzymes involved in the 7 alpha-hydroxylation/dehydroxylation pathway for the biosynthesis of cholestanol are probably located in the liver. Both 7 alpha-hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one may be intermediates.
AuthorsS Skrede, I Björkhem, M S Buchmann, T Midtvedt
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 260 Issue 1 Pg. 77-81 (Jan 10 1985) ISSN: 0021-9258 [Print] United States
PMID3917436 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bile Acids and Salts
  • Carbon Radioisotopes
  • Tritium
  • Cholestanol
  • Cholesterol
Topics
  • Animals
  • Bile Acids and Salts (metabolism)
  • Biliary Fistula (metabolism)
  • Carbon Radioisotopes
  • Cecum (metabolism)
  • Cholestanol (biosynthesis, metabolism)
  • Cholesterol (analogs & derivatives, metabolism)
  • Germ-Free Life
  • Intestine, Small (metabolism)
  • Liver (metabolism)
  • Male
  • Rabbits
  • Rats
  • Species Specificity
  • Tritium

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