It is well established that high levels of serum cholesterol

It is well established that high levels of serum cholesterol may place people at an increased risk for coronary artery disease. A diet high in saturated fat contributes to elevation of serum cholesterol, particularly in the form of low-density-lipoproteins (LDLs). But cholesterol levels are determined by genetic factors as well. In familial hypercholesterolemia (FH), patients have a mutation in either the gene that encodes the LDL receptor (LDLR) or in the gene for Apolipoprotein B (ApoB) that is part of the LDL particle itself and recognized by the receptor LDLR.

FH is a recessive disease so that people who have one mutant copy of either the LDL receptor or ApoB gene have elevated serum cholesterol and often develop early heart disease (in their 30s or 40s). In contrast patients with two mutant copies of the genes have extremely high serum cholesterol and often will develop severe coronary artery disease in their 20s. ( 7 points total)

Questions:

1) A patient is suffering from FH. His fibroblasts are cultured and exposed to ferritin-labeled LDL particles at 4°C. When observed in the electron microscope, these cells are seen to have the ferritin-labeled LDL particles spread uniformly over the cell surface. What is the basis of his disease?

Solution

The cells of the patient suffeing from FH are not able to internalize the serum LDL particles .It is able to bind to the LDL receptors (LDLR) ,but cannot be localized to the coated pits,the place where internalization takes place.Therefore, the cells of the patient suffering from FH are not able to take up LDL particles ,which can be seen in the electron microscope.