Cholesterol is present in several different forms in the body. It is synthesized by the liver and is carried throughout the blood by high-density lipoproteins (HDL), or “good cholesterol. ” Alternatively, it can be transported by low-density lipoproteins (LDL) or so-called “bad cholesterol.” Molecules that bind compounds and are triggered to act by this binding are known as receptors. A low-density lipoprotein receptor is a special lipoprotein receptor that binds LDL and transports it inside of the cell.
Although often considered in a negative light, cholesterol is required for proper cellular function. It is a critical component of cellular membranes. There are a number of different forms of cholesterol. The ones that are most commonly subject to medical testing are cholesterol units bound to special proteins that transport fats throughout the blood. These proteins are known as lipoproteins, and are composed of proteins and lipids—compounds that do not dissolve in water and fold inward to carry the fats.
High-density lipoproteins scavenge cholesterol from tissues and return it to the liver. From there, it is reabsorbed into the liver. For this reason, it is known as “good cholesterol.” In contrast, low-density lipoproteins transport cholesterol from the liver throughout the bloodstream. This is the cholesterol that is linked with heart attacks and certain types of strokes. For this reason, LDL is known as “bad cholesterol.”
These lipoproteins require the presence of a lipoprotein receptor for them to be able to bind to cells. This receptor is a molecule on the cell’s surface that binds to the lipoprotein. In particular, the low-density lipoprotein receptor has been highly studied, since the amounts of LDL correlate with diseases.
The protein that comprises the low-density lipoprotein receptor is highly complex and is composed of a number of individual domains, most with different functions. This receptor is contained within pits on the surface of the cell, primarily on the liver. Once it has bound LDL, it is taken up within the cell in a process known as endocytosis—-an important pathway for absorbing membranes. The LDL inside of the cell is degraded to release the fats, and the receptor either returns to the surface of the cell or is destroyed.
Most of the cholesterol found in a person is synthesized by the liver in response to a diet high in saturated fats. When the liver has accumulated too much cholesterol, it stops making the low-density lipoprotein receptor. Thus, LDL accumulate in the blood. The drug class known as statins can help prevent this from happening by preventing the liver from making cholesterol.
There is a hereditary genetic defect for the low-density lipoprotein receptor in which LDL cannot be properly taken out of the patient's blood, and thus has a greatly increased chance of experiencing severe cardiac issues by middle age. This condition is referred to as familial hypercholesterolemia. During the process of studying this disease, the researchers Brown and Goldstein discovered the low-density lipoprotein receptor. This caused them to discover the pathway of having endocytosis regulated by receptors. These researchers were awarded the Nobel Prize for their findings.
