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 compositions of different membranes througout the mammalian cell. As she expected, the lipid composition gradually changes from predominantly glycerophospholipid in the ER to equal glycerophospholipid/sphingolipid in the plasma membrane of normal or untreated cells (white bars). Following treatment with her drug (black bars), she is surprised that there is a significant change in the glycerophospholipid content within the cellular membranes.

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

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

c) Hypothesize as to which protien/enzyme this drug inhibits.

d) Would this be a good treatment for patients who have blood-clotting disorders? Why or why not?

Explanation / Answer

a) (PS) phosphatidylserine is completely inhibited in the plasma membrane upon drug treatment

b) Drug might cleaves the glycerophospholipids like PS, PC and PE into its precursor molecule called PA (phosphatidic acid) and serine, choline and ethanolamine respectively. Hence, we could see more PA with drug treatment than untreated.

c) Choline/ethanolamine phosphotransferase might be inhibited by the drug that prevents the CDP-choline/ethanolamine conjugation to DAG to from PS/PE.

d) It would not be appropriate for the patients with a blood-clotting disorder, since, this drug prevents phospholipids synthesis of various blood cells including platelets which are key blood cells for clotting. If drug exacerbates the defective formation of platelets that leads to longer time taken for clotting or prevention.   

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