Why can defective LDL receptors lead to hypercholesterolemia?

Defective LDL receptors can indeed lead to hypercholesterolemia primarily because they prevent cholesterol from entering cells, thereby resulting in elevated blood cholesterol levels. LDL (low-density lipoprotein) receptors are essential for the endocytosis of LDL particles, which carry cholesterol from the bloodstream into cells. When LDL receptors are functioning properly, they bind to LDL particles, facilitating their uptake and thus lowering circulating cholesterol levels.

When these receptors are defective, the cells are unable to effectively remove LDL from the bloodstream. This inefficiency leads to an accumulation of LDL in the blood, contributing to hypercholesterolemia. High blood cholesterol levels can increase the risk of atherosclerosis and cardiovascular diseases. Therefore, the inability of cells to take up LDL due to defective receptors is a key mechanism by which hypercholesterolemia occurs.

This shows how critical the role of LDL receptors is in maintaining cholesterol homeostasis in the body.