Biosynthesis of cholestanol from intestinal 7 alpha-hydroxy-4-cholesten-3-one.
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| Abstract |
Using isotope dilution-mass spectrometry, it was shown that human bile contains significant amount of 7 alpha-hydroxy-4-cholesten-3-one, an intermediate in the major pathway for bile acid biosynthesis. In bile from 14 healthy subjects, the concentration was 0.14 +/- 0.01 micrograms/ml (mean +/- S.E.). Four bile samples collected from two patients with cerebrotendinous xanthomatosis contained considerably higher amounts of this steroid, 0.47-1.32 micrograms/ml. After oral administration of [4-14C]7 alpha-hydroxy-4-cholesten-3-one to rabbits, 14C-labeled cholestanol could be isolated from the intestinal wall, liver, and blood after 24 h. The label incorporated into the intestinal wall was about 10% of that obtained with [4-14C]cholesta-4,6-dien-3-one or [4-14C]4-cholesten-3-one as precursors. Labeled cholesta-4,6-dien-3-one and 4-cholesten-3-one could be isolated from the intestinal contents 12 h after feeding [4-14C]7 alpha-hydroxy-4-cholesten-3-one to rabbits. It is proposed that cholesta-4,6-dien-3-one and 4-cholesten-3-one are formed from 7 alpha-hydroxy-4-cholesten-3-one by the same mechanism as that involved in 7 alpha-dehydroxylation of primary bile acids. We suggest that biliary 7 alpha-hydroxy-4-cholesten-3-one may be a physiological precursor to cholestanol. The possibility is discussed that part of the increased formation of cholestanol in patients with cerebrotendinous xanthomatosis is due to excess biliary 7 alpha-hydroxy-4-cholesten-3-one or some metabolite of this steroid.
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| Authors | S Skrede, I Björkhem |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 257 Issue 14 Pg. 8363-7 (Jul 25 1982) ISSN: 0021-9258 [Print] United States |
| PMID | 7045120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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