13-100 Cholesterol is an essential component of the plasma membrane, but people who have very high levels of cholesterol in their blood (hypercholesterolemia) tend to have heart attacks. Blood cholesterol is carried in the form of cholesterol esters in low-density lipoprotein (LDL) particles. LDL binds to a high-affinity receptor on the cell surface, enters the cell via a coated pit, and ends up in lysosomes. There its protein coat is degraded, and cholesterol esters are released and hydrolyzed to cholesterol. The released cholesterol enters the cytosol and inhibits the enzyme HMG CoA reductase, which controls the first unique step in cholesterol biosynthesis. Patients with severe hypercholesterolemia cannot remove LDL from the blood. As a result, their cells do not turn off normal cholesterol synthesis, which makes the problem worse. LDL metabolism can be conveniently divided into three stages experimentally: binding of LDL to the cell surface, internalization of LDL, and regulation of cholesterol synthesis by LDL. Skin cells from a normal person and two patients suffering from severe familial hypercholesterolemia were grown in culture and tested for LDL binding, LDL internalization, and LDL regulation of cholesterol synthesis. The results are shown in Figure 13-19. LDL bound (ug/g cell protein) LDL internalized (µg/g cell protein) cholesterol synthesis (nmol/hr) 0.2 normal 0.1 0.0 tooe 1.0 (A) BINDING (B) INTERNALIZATION normal 146 FH 50 100 0 50 100 0.5 FH 0 50 100 0.0000 0 0.2 0.0 0.400 (C) REGULATION 0 FH normal normal 0 50 100 50 100 0 LDL (μg/mL) normal JD JD normal 50 100 LDL (µg/mL) Figure 13-19 LDL metabolism in normal cells and in cells from patients with severe familial hypercholesterolemia (Problem 13-100). (A) Surface binding of LDL. Assays at 4°C allow binding but not internalization. (B) Internalization of LDL. After binding at 4°C, the cells are warmed to 37°C. Binding and uptake of LDL can be followed by labeling LDL either with ferritin particles, which can be seen by electron microscopy, or with radioactive iodine, which can be measured in a gamma counter. (C) Regulation of cholesterol synthesis by LDL

13-100 Cholesterol is an essential component of the plasma membrane, but people who have very high levels of cholesterol in their blood (hypercholesterolemia) tend to have heart attacks. Blood cholesterol is carried in the form of cholesterol esters in low-density lipoprotein (LDL) particles. LDL binds to a high-affinity receptor on the cell surface, enters the cell via a coated pit, and ends up in lysosomes. There its protein coat is degraded, and cholesterol esters are released and hydrolyzed to cholesterol. The released cholesterol enters the cytosol and inhibits the enzyme HMG CoA reductase, which controls the first unique step in cholesterol biosynthesis. Patients with severe hypercholesterolemia cannot remove LDL from the blood. As a result, their cells do not turn off normal cholesterol synthesis, which makes the problem worse. LDL metabolism can be conveniently divided into three stages experimentally: binding of LDL to the cell surface, internalization of LDL, and regulation of cholesterol synthesis by LDL. Skin cells from a normal person and two patients suffering from severe familial hypercholesterolemia were grown in culture and tested for LDL binding, LDL internalization, and LDL regulation of cholesterol synthesis. The results are shown in Figure 13-19. LDL bound (ug/g cell protein) LDL internalized (µg/g cell protein) cholesterol synthesis (nmol/hr) 0.2 normal 0.1 0.0 tooe 1.0 (A) BINDING (B) INTERNALIZATION normal 146 FH 50 100 0 50 100 0.5 FH 0 50 100 0.0000 0 0.2 0.0 0.400 (C) REGULATION 0 FH normal normal 0 50 100 50 100 0 LDL (μg/mL) normal JD JD normal 50 100 LDL (µg/mL) Figure 13-19 LDL metabolism in normal cells and in cells from patients with severe familial hypercholesterolemia (Problem 13-100). (A) Surface binding of LDL. Assays at 4°C allow binding but not internalization. (B) Internalization of LDL. After binding at 4°C, the cells are warmed to 37°C. Binding and uptake of LDL can be followed by labeling LDL either with ferritin particles, which can be seen by electron microscopy, or with radioactive iodine, which can be measured in a gamma counter. (C) Regulation of cholesterol synthesis by LDL

Biology 2e

2nd Edition

ISBN:9781947172517

Author:Matthew Douglas, Jung Choi, Mary Ann Clark

Publisher:Matthew Douglas, Jung Choi, Mary Ann Clark

Chapter3: Biological Macromolecules

Section: Chapter Questions

Problem 14RQ: Cholesterol is an integral part of plasma membranes. Based on its structure, where is it found in...

See similar textbooks