PMID: 2099041Jan 1, 1990Paper

Familial hypercholesterolemia: dissection of a receptor disease

Zeitschrift für Kardiologie
W J Schneider

Abstract

In 1973, studies with cultured human fibroblasts by Brown, Goldstein, and colleagues showed that receptor-mediated endocytosis of low-density lipoprotein (LDL) is the regulatory principle in cellular cholesterol homeostasis. The complete sequence of metabolic events associated with the binding, uptake, and degradation of these cholesterol-rich lipoprotein particles by mammalian cells has been termed the LDL receptor pathway. This important process has two main tasks. First, it supplies cells with cholesterol, thereby mediating the removal of cholesterol-rich lipoproteins from the circulation. Second, it protects cells from over-accumulation of cholesterol, because the cholesterol derived from lysosomal hydrolysis of LDL cholesterylesters exerts a series of feedback control mechanisms designed to maintain a constant level of cholesterol within the cell. Thus, high extracellular concentrations of LDL reduce cellular synthesis of cholesterol (by suppression of the activities of 3 hydroxy-, 3-methyl-glutaryl-CoA synthase and reductase, rate-limiting enzymes in cholesterol synthesis), stimulate its re-esterification, and decrease the number of LDL receptors, preventing further cellular entry of cholesterol. The suppression of LDL re...Continue Reading

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.