Dr. Williams is interested in studying the effect of a certain drug on the lipid

Question

Dr. Williams is interested in studying the effect of a certain drug on the lipid composition of different membranes throughout the mammalian cell. As she expected, the lipid composition gradually changes from predominately glycerophospholipid in the ER to equal glycerophospholipid/sphingolipid in the plasma membrane of normal or unrelated cells (white bars). Following treatment with her drug (grey bars), she is surprised that there is a significant change in the glycerophospholipid content within the cellular membranes.

The lipid compositional data shown in the graphs are expressed as a percentage of the total phospholipid mammalian cells. PCm phosphatidyl choline; PE, phosphatidyl ethanolamine; Pl, phosphatidyl inositol; PS, phosphatidyl serine; PA, phosphatidic acid; SM, sphingomyelin.

a. The presence of which glycerophospholipid is altered the most by treatment of this drug within the plasma membrane?

b. Why is the phosphatidic acid increased within the ER membrane following drug treatment compared to normal cells?

c. Hypothesize as to which protein/enzyme this drug inhibits.

Explanation / Answer

a. phosphatidyl ethanolamine is the glycerophospholipid most affected in the plasma membrane.

b. phosphatidic acid is increased within the ER membrane because the step converting PA to other lipid products is inhibited.

c. lipid phosphate phosphohydrolases is inhibited by this drug. It inhibits conversion to DAG.

d. This would be a good treatment for blood clotting disorders because PA binds preferentially to factor VIIa and activated prtoein C whcih are vital in blood clotting process.

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