how can i do point b and d 13-100 Cholesterol is an essential component of the plasma membrane, but people who havevery high levels of cholesterol in their blood (hypercholesterolemia) tend to have heartattacks. 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 acoated pit, and ends up in lysosomes. There its protein coat is degraded, and cholesterol estersare released and hydrolyzed to cholesterol. The released cholesterol enters the cytosol andinhibits the enzyme HMG CoA reductase, which controls the first unique step in cholesterolbiosynthesis. 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 problemworse. LDL metabolism can be conveniently divided into three stages experimentally: bindingof 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 familialhypercholesterolemia 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.(ug/g cell protein)LDL internalized(pg/g cell protein)cholesterol synthesis(nmol/hr)0.2 normal0.10.0 tooe(A) BINDING1.00.000000.20 50 100(8) INTERNALIZATIONnormal1240.5FH50 100 00.004000FH(C) REGULATION0FHnormalnormal0JD50 100normalJD50 100JDnormal50 100 0 50 100LDL (μg/mL)LDL (g/mL)Figure 13-19 LDL metabolism in normal cells and in cells from patientswith severe familial hypercholesterolemia (Problem 13-100). (A) Surfacebinding of LDL. Assays at 4°C allow binding but not internalization.(B) Internalization of LDL. After binding at 4°C, the cells are warmed to37°C. Binding and uptake of LDL can be followed by labeling LDL eitherwith ferritin particles, which can be seen by electron microscopy, or withradioactive iodine, which can be measured in a gamma counter.(C) Regulation of cholesterol synthesis by LDLB. In Figure 13-19B, internalization of LDL by normal cells increases as the externalLDL concentration is increased, reaching a plateau 5-fold higher than the amountof externally bound LDL. Why does LDL enter cells from patients FH or JD at such aslow rate?C. In Figure 13-19C, the regulation of cholesterol synthesis by LDL in normal cells iscompared with that in cells from FH and JD. Why does increasing the external LDLconcentration inhibit cholesterol synthesis in normal cells, but affect it only slightlyin cells from FH or JD?D. How would you expect the rate of cholesterol synthesis to be affected if normalcells and cells from FH or JD were incubated with cholesterol itself? (Freecholesterol crosses the plasma membrane by diffusion.

Familial hypercholesterolemia is a genetic disorder occurring due to the aberration in chromosome…

(A) BINDING 0.2 normal normal #A FH 50 100 0 bound (g/g cell protein) LDL LDL internal (µg/g cell 0.1- 0.0 9 0.5 0.0 fal (B) INTERNALIZATION 0.2 0.0 0.4+000 normal FH (C) REGULATION 50 1000 50 100 FH 100 normal normal normal 50 1000 50 100 LDL (g/mL) LDL (ug/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 B. In Figure 13-19B, internalization of LDL by normal cells increases as the external LDL concentration is increased, reaching a plateau 5-fold higher than the amount of externally bound LDL. Why does LDL enter cells from patients FH or JD at such a slow rate? C. In Figure 13-19C, the regulation of cholesterol synthesis by LDL in normal cells is compared with that in cells from FH and JD. Why does increasing the external LDL concentration inhibit cholesterol synthesis in normal cells, but affect it only slightly

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...