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Steroid Requirements for Suppression of HMG CoA Reductase Activity in Cultured Human Fibroblasts

  • Joseph L. Goldstein
  • Jerry R. Faust
  • Gloria Y. Brunschede
  • Michael S. Brown
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 63)

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).

Keywords

Cholesteryl Ester Cholesterol Synthesis High Density Lipoprotein Familial Hypercholesterolemia Keto Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • Joseph L. Goldstein
    • 1
  • Jerry R. Faust
    • 1
  • Gloria Y. Brunschede
    • 1
  • Michael S. Brown
    • 1
  1. 1.Department of Internal Medicine, Southwestern Medical SchoolUniversity of TexasDallasUSA

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