CAS BI 203 Lecture Notes - Lecture 2: Familial Hypercholesterolemia, Ldl Receptor, Hypercholesterolemia
Document Summary
Monolayers of cultured fibroblasts from normal human subjects bind. I-labeled low-density lipoproteins with high affinity and specificity. High affinity binding wasn"t observed in cells from 5 unrelated subjects w. homozygous form of familial hypercholesterolemia. In normal cells incubated at 37degrees, the binding sites were saturated at a low-density lipoprotein concentration of 20. A max of 250k molecules could be bound to each cell. 3-hydroxy-3-mythylglutaryl (hmg coa) is a rate-controlling enzyme in cholesterol biosynthesis. In fibroblasts cultured from normal human subjects the activity of. Hmg coa (the rate controlling enzyme in cholesterol biosynthesis) is regulated by the content of low-density lipoproteins (ldl) & vldl in the culture medium. Cultured fibroblasts from normal subjects take up ldl by a temp- dependent process that is highly specific, reaches an equilibrium w. time, and is saturable at low levels of ldl. The degree of suppression of hmg coa reductase activity is proportional to the amount of ldl bound.
