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Encyclopedia of Physical Science and Technology EN008C-380 June 29, 2001 16:42

654 Lipoprotein/Cholesterol Metabolism

TABLE V Lipoprotein Receptors
Name Ligands Tissue locations
LDL receptor (LDLR) LDL, apo-E, hepatitis C virus, Rous sarcoma virus subgroup A, Ubiquitously expressed
human rhinovirus
LDL receptor-related protein/ Apo-E, lipoprotein lipase, hepatic lipase, thrombospondin, Liver, brain, lung, adrenal, intestine,
α 2 -macroglobulin receptor (LRP) Pseudomonas exotoxin A, α 2 -macroglobulin, kidney, placenta, ovary, testis
receptor-associated protein (RAP), lactoferrin, t-PA,
u-PA, t-PA:PAI-1, u-PA:PAI-1, elastase-a1-antitrypsin
VLDL receptor apo-E, Reelin Smooth muscle, brain, adipose, adipose,
adrenal, testis, ovary, placenta, lung
gp330/megalin (VLDLR) LDL, apo-J/clusterin, apolipoproteinH/β2-glycoprotein-I, Kidney, lung, thyroid, parathyroid,
PAI-1, prourokinase, lipopoprotein lipase, aprotinin, epididymis, ileum, placenta, thymus
transcobalamin-vitamin B12, vitamin D-binding protein,
retinol-binding protein, PTH, insulin, β2-microglobulin,
epidermal growth factor, prolactin, lysozyme,
cytochrome c, thyroglobulin, plasminogen, albumin,
polybasic drugs, RAP, Ca 2+
Apo-E receptor R2 (apoER2; LR7/8B) Apo-E, apo-B100, Reelin, RAP Brain, testes, ovary, placenta

of ligands, including senescent neutrophils, collagen, and receptors. The discovery of LDL oxidation and its impli-
malaria-infected erythrocytes. cations for atherosclerosis has ignited a strong interest in
the potential role of dietary antioxidants (e.g., vitamins C
and E) in the prevention of atherosclersosis.
F. An HDL Receptor, SR-B1
Three scavenger receptors for oxidized LDL have been
Unlike LDL, HDL can deliver cholesterol to certain tis- identified; SR-A1, SR-A2, and CD36 (Table VI). These
sues (liver and steroidogenic tissues like adrenal, ovary, receptors have also been implicated in the phagocytosis
and leydig cells) without the HDL particle being internal- of damaged or apoptotic blood cells (e.g., lymphocytes
ized. The SR-B1 protein mediates the docking of HDL and erythrocytes). CD36 has been implicated in fatty acid
with cells and the delivery of cholesterol ester from the uptake into cells. The scavenger receptors can bind a wide
core of the HDL particle to the cells. This receptor is in array of molecules other than lipoproteins (e.g., polyan-
the scavenger receptor family and is able to bind other ions, oligonucleotides, bacterial endotoxin, and crocido-
lipoproteins in addition to HDL. lite asbestos).
The discovery that LDL receptor deficiency in famil-
ial hypercholesterolemia is associated with premature
atherosclerosis was initially paradoxical. A hallmark of XI. HDL AND “REVERSE
atherosclerotic lesions is the formation of “foam cells”— CHOLESTEROL TRANSPORT”
macrophages and smooth muscle cells that accumulate
cytoplasmic cholesterol ester droplets. If these cells lack Epidemiological studies show a strong inverse relation-
the LDL receptor, how do they import excessive amounts ship between HDL levels (HDL cholesterol or apo-A1)
of cholesterol? and risk of CHD. Even a small increase in HDL is signifi-
Chemical modification of LDL (e.g., acetylation) abol- cantly correlated with a reduction in the risk of premature
ishes its ability to bind to the LDL receptor. However, the heart disease.
modified LDL binds to other cell surface receptors, termed Unlike VLDL and chylomicrons, HDL is formed from
scavenger receptors. Unlike the LDL receptor, scavenger its protein and lipid components in the bloodstream and
receptors are not downregulated by cholesterol. Like the interstitial fluids. The major apolipoproteins of HDL are
LDL receptor, uptake through scavenger receptors leads to apo-A1 and apo-A2. These proteins are secreted from hep-
accumulation of LDL-derived cholesterol as cytoplasmic atocytes and intestinal epithelial cells independently and
cholesterol ester droplets. also as minor components of VLDL and chylomicrons.
Are there any physiological counterparts to in vitro Apo-A1 and apo-A2 bind to phospholipids. Phospholipids
chemical modification of LDL? The polyunsaturated fatty are available from the surface of VLDL after lipolysis. In
acylchainsofLDLlipidscanbeoxidized,leadingtocleav- addition, cells are able to efflux phospholipids through the
age and formation of chemically reactive short-chain fatty action of ABCA1.
aldehydes. These aldehydes react with the protein moiety ABCA1 is a membrane transport protein belonging to
of LDL, apo B-100, converting it to a ligand for scavenger a large family of ATP-binding cassette proteins. These