Abstract
The rate of cholesterol synthesis in cultured human fibroblasts is determined by the activity of 3-hydroxy-3-methylglutary1 coenzyme A reductase (HMG CoA reductase) (1–3). The activity of this enzyme in normal fibroblasts becomes suppressed when low density lipoproteins (LDL) bind to specific receptors on the cell surface (4, 5) and deliver cholesterol and cholesteryl esters to the cell (6). High density lipoproteins (HDL), which do not bind to the LDL receptor (4, 5), do not increase the cellular content of cholesterol and cholesteryl esters (6) nor do they suppress HMG CoA reductase activity and cholesterol synthesis (1, 3). Cultured fibroblasts from subjects with the autosomal dominant disorder familial hypercholesterolemia are deficient in the LDL receptor (4, 5, 7). As a result, LDL does not bind to the cells (4, 5, 7), cholesterol is not transferred intracellularly (6), HMG CoA reductase activity is not suppressed, and cholesterol is overproduced (2, 3).
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References
Brown, M. S., Dana, S. E., and Goldstein, J. L. Proc. Nat. Acad. Sci. USA 70: 2162–2166, 1973.
Goldstein, J. L. and Brown, M. S. Proc. Nat. Acad. Sci. USA 70: 2804–2808, 1973.
Brown, M. S., Dana, S. E., and Goldstein, J. L. J. Biol. Chem. 249: 789–796, 1974.
Brown, M. S. and Goldstein, J. L. Proc. Nat. Acad. Sci. USA 71: 788–792, 1974.
Goldstein, J. L. and Brown, M. S. J. Biol. Chem., in press.
Brown, M. S., Dana, S. E., and Goldstein, J. L. Proc. Nat. Acad. Sci. USA, in press, 1974.
Brown, M. S. and Goldstein, J. L. Science 185: 61–63, 1974.
Brown, M. S. and Goldstein, J. L. J. Biol. Chem., in press, 1974.
Kandutsch, A. A. and Chen, H. W. J. Biol. Chem. 248:8408–8417, 1973.
Chicoye, E., Powrie, W. D., and Fennema, O. Lipids 3: 551–556, 1968.
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© 1975 Plenum Press, New York
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Goldstein, J.L., Faust, J.R., Brunschede, G.Y., Brown, M.S. (1975). Steroid Requirements for Suppression of HMG CoA Reductase Activity in Cultured Human Fibroblasts. In: Kritchevsky, D., Paoletti, R., Holmes, W.L. (eds) Lipids, Lipoproteins, and Drugs. Advances in Experimental Medicine and Biology, vol 63. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-3258-9_5
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DOI: https://doi.org/10.1007/978-1-4684-3258-9_5
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