Answer Happy

Please answer all parts (a-e) of the question as it is allone.
4. Endocytosis: Cholesterol is an essential component of the plasma membrane, but people who have very high levels of cholesterol in their blood tend to have heart attacks. Cholesterol in the blood is carried in the form of low density lipoprotein (LDL) particles. LDL binds to a high affinity receptor on the cell surface (LDL receptor), enters the cell via a coated pit, and ends up in lysosomes. In the lysosome its protein coat is degraded and cholesterol esters are released and hydrolysed to cholesterol. The released cholesterol enters the cytosol and inhibits the enzyme HMG CoA reductase, which controls the committed step in cholesterol synthesis. 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 (through the LDL receptor), internalization of LDL, and regulation of cellular synthesis of LDL. Skin cells from a normal person and two patients suffering from severe familial hypercholestolemia were grown in culture and tested for LDL binding, LDL internalization, and LDL regulation of cholesterol synthesis. The results are shown below: LDL Bound (ug/g cell protein) LDL internalization (ug/g cell protein Cholesterol synthesis (nmol/hr) A B C A B с Normal FH JD LDL (ug/ml) LDL (ug/ml) a. For the graphs labeled "A": In the binding assay, the surface binding of LDL by normal cells is compared with LDL binding by cells from patients FH and JD. Why does binding by normal cells and by JD's cells reach a plateau? Given the introductory information how can you explain what is going on at the cell surface that would cause the graph to plateau. Remember what you learned about carrier proteins and saturation kinetics with regard to membrane transport! (1 points).

(b.)What explanation can you suggest for the lack of LDL binding by FH's cells? Rubric: Why can't FH's cells bind LDL? (.5 point) c. For the graphs labeled "B": Internalization of LDL by normal cells increases as the external LDL concentration is increased, reaching a plateau five fold higher than the amount of externally bound LDL. Why does LDL not enter the cells of FH or JD? Grading rubric: First consider your analysis from "a" for both FH and JD. This will allow you to differentiate between why PH is unable to internalize LDL (0.25 points) vs lack of internalization of LDL inJD (0.25 points). d. For the graphs labeled "C": The regulation of Cholesterol synthesis by LDL in normal cells is compared with cells from FH and JD. Why does increasing external LDL concentration inhibit cholesterol synthesis in normal cells but not affect it in cells from FH and JD? Grading rubric: Again, consider your analysis of "a" and "b" to conclude why both FH and JD cells cannot inhibit cholesterol biosynthesis in the presence of high levels of LDL (1 point). e. How would you expect the rate of cholesterol synthesis to be affected if normal cells and cells from FH or JD were incubated with free cholesterol (free cholesterol can diffuse across the plasma membrane!). Grading rubric: Would incubating with free cholesterol correct the problem or not (0.5 points)? Explain why (0.5points).