Question

Why do you think we chose to test the compounds Amiloride, Nystatin and Chlorpromazine for cholesterol fibroblast uptake in patients without LDL receptors (hypercholeterolemia)? What do you they have in common? Suggest one more compound that you would like to test to cure this disease.

what is the mechanism that fibroblasts with the pathology studied use to uptake abnormal levels of cholesterol? Is this a receptor mediated mechanism or unspecific?

Answer 1

In Ldl receptor defecient people, fibroblasts unable to uptake LDL from blood. Hence hyper cholesterol resulted. The drugs like Amiloride nystatin and chlorpromazine are reported to reduce cholesterol levels in blood by mobilising either by binding with it or by increasing their uptake. Hence they tested to treat patients suffering from no LDL receptors in their blood. Statins like lovastatin, atoravastatin, pravastatin etc could also be used to test the ldl deficient people.

In patients suffering from the above condition are unable to synthsise LDL receptor, hence the plasma LDL cannot be absorbed by fibroblast cells. Hence LDL accumulates in blood leading hypercholesteromea. The specific receptor mediated cholesterol uptake mechanism is absent in them. By treating with drugs above dicreases cholesterol levels using unspecific mechanisms either by binding with it (amiloride, nystatin use this mechanism) or by dicreasing the circulating cholesterol levels by inhibiting cholesterol synthesising enzymes (chlorpromazine use this mechanism).