Cholesterol is an essential component of the plasma membrane, but people who hav
ID: 68298 • Letter: C
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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 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 in inhibits me enzyme HMG CoA reductase, which controls the committed 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 convenicently divided into three stages experimentally: binding of LDL to the cell surface, internalization of LDL, and regulation of cellular synthesis by LDL. Skin cells form a normal person and two patterns 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 the figures. In Figure A. the surface binding of LDL by normal cells is compared with LDL binding by cells from FH and JD. Why does binding by normal cells and by JD's cells teach a plateau? What explanation can you suggest for the luck of LDL binding by FH's cells? Figure A) High-affinity surface binding of LDL In Figure B, internalization of LDL by normal cells increases as the external LDL concentration is increased, reaching a plateau fivefold higher than the amount of externally bound LDL. Why does LDL not enter cells from FH or JD? Figure B) Internalization of LDLExplanation / Answer
Figure A:
From the figure, it is observed that the cells from FH patient does not bind to LDL. This means it has no affinity for LDL and this could be due to mutation in the LDL receptor, making it completely defective. In case of JD, since the patient is suffering from hypercholesterolemia, it suggests certain mutation in the receptor, which probably lowers the affinity for LDL, but is able to bind LDL, at lower than the normal levels. Another possibility is the number of receptors for LDL in JD cells would be lower than the normal cells.
The JD patient cells and normal persons cells show a plateau for LDL binding. This suggests that the receptors for LDL on both type of cells are saturated with LDL, and cannot bind any more molecules of LDL.
Figure B: The functioning of LDL receptors in JD & FH is compromised due to genetic mutations linked with hypercholesterolemia. As a result of poor binding and functioning of the receptors, the cells exhibit very slow or no formation of the coated pit for internalization of LDL molecules. Hence, even with the increase in external LDL, it does not get internalized in the cells from JD and FH.
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