A 38-year-old man in a rural area presents to a physician to follow up an infection. Ocular examination reveals small opaque rings on the lower edge of the iris in the anterior chamber of the eye. Nodular lesions are found on his achilles tendon. Successful therapy should be aimed at increasing which of the following gene products in hepatocyte cell membranes?
This man has characteristic signs of familial hypercholesterolemia, an autosomal dominant disorder affecting about 1 in 500 persons. The xanthomas on the Achilles tendon and the arcus lipoides (the opaque rings in the eye) are pathognomonic. Affected individuals have very high LDL cholesterol because of deficient endocytosis of LDL paicles by LDL receptors. These receptors recognize the apo B-100 protein cotranspoed with cholesterol esters in LDL. Treatments aim at increasing genetic expression of LDL receptors (i.e., apo B-100 receptors) to enhance clearance of LDL paicles. Dietary changes, a resin drug, niacin, or an HMG-CoA reductase inhibitor could be tried. Apo B-100 is the apoprotein of liver-produced lipoproteins such as VLDL, IDL and LDL. It is therefore not in the hepatic cell membranes, and it might be expected to decrease with decreasing concentrations of circulating LDL. Apo E is an apoprotein found on VLDL, IDL, and chylomicrons, allowing "scavenging" by the liver of remnants or of the lipoprotein itself. It is not found in the hepatocyte membrane. Apo E receptor would actually be increased by the treatment with hypocholesterolemic agents. However, the apo E receptor is not involved in the scavenging of LDL paicles.
Apo B-100
Apo B-100 receptor
Apo E
Apo E receptor