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| Item Type: | Article |
|---|---|
| Title: | Markedly reduced bile acid synthesis but maintained levels of cholesterol and vitamin D metabolites in mice with disrupted sterol 27-hydroxylase gene |
| Creators Name: | Rosen, H., Reshef, A., Maeda, N., Lippoldt, A., Shpizen, S., Triger, L., Eggertsen, G., Bjorkhem, I. and Leitersdorf, E. |
| Abstract: | Sterol 27-hydroxylase is important for the degradation of the steroid side chain in conversion of cholesterol into bile acids and has been ascribed a regulatory role in cholesterol homeostasis. Its deficiency causes the autosomal recessive disease cerebrotendinous xanthomatosis (CTX), characterized by progressive dementia, xanthomatosis, and accelerated atherosclerosis. Mice with a disrupted cyp27 (cyp27(-/-)) had normal plasma levels of cholesterol, retinol, tocopherol, and 1,25-dihydroxyvitamin D. Excretion of fecal bile acids was decreased (<20% of normal), and formation of bile acids from tritium-labeled 7alpha-hydroxycholesterol was less than 15% of normal. Compensatory up-regulation of hepatic cholesterol 7alpha-hydroxylase and hydroxymethylglutaryl-CoA reductase (9- and 2-3-fold increases in mRNA levels, respectively) was found. No CTX-related pathological abnormalities were observed. In CTX, there is an increased formation of 25-hydroxylated bile alcohols and cholestanol. In bile and feces of the cyp27(-/-) mice only traces of bile alcohols were found, and there was no cholestanol accumulation. It is evident that sterol 27-hydroxylase is more important for bile acid synthesis in mice than in humans. The results do not support the contention that 27-hydroxylated steroids are critical for maintenance of cholesterol homeostasis or levels of vitamin D metabolites in the circulation. |
| Keywords: | Bile, Bile Acids and Salts, Carotenoids, Cerebrotendinous Xanthomatosis, Cholestanetriol 26-Monooxygenase, Cholesterol, Cytochrome P-450 Enzyme System, Feces, Gas Chromatography-Mass Spectrometry, Gene Targeting, Hydroxycholesterols, Steroid Hydroxylases, Sterols, Vitamin D, Vitamins, Animals, Mice |
| Source: | Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Volume: | 273 |
| Number: | 24 |
| Page Range: | 14805-14812 |
| Date: | June 1998 |
| Official Publication: | https://doi.org/10.1074/jbc.273.24.14805 |
| PubMed: | View item in PubMed |
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