Plasma lipoproteins are spherical complexes of lipids and apoproteins. They include chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and high-density lipoproteins. These differ in size, composition, and density.
Lipoproteins transport lipids throughout the body and keep them soluble as they do so. As we age, lipoproteins gradually build up in tissues and contribute to atherosclerosis.
Lipoproteins are composed of a lipid core, containing TAG and cholesterol esters, and an outer shell made up of amphipathic apoproteins, phospholipid, and nonesterified cholesterol. Lipoprotein contents are constantly being passed from one to another, making the distinction between classes somewhat variable.
Lipids are transported in the blood bound to various lipoproteins.
| Composition | Apo proteins | |||
|---|---|---|---|---|
| Chylomicrons | mostly TAG | B48, C-II, E | ||
| VLDL | 50% TAG | B-100, C-II, E | ||
| LDL | 50% cholesterol | B-100 | ||
| HDL | 50% protein | A, C, E |
HDL and LDL now have their own page...
Chylomicrons are assembled in intestinal mucosal cells and contain TAG, cholesterol, and fat-soluble vitamins.
Apoprotein B-48 is unique to chylomicrons. It is termed B-48 because it contains only 48% of the entire apo B protein (cf apo B-100 from VLDL and LDL). This occurs via post-transcriptional editing of the mRNA to create a nonsense stop codon.
During apo B-48 movement from the ER to the Golgi, it is loaded with lipid. This forms secretory vesicles that fuse with the plasma membrane and are released into the lymphatic system.
Once in the plasma, chylomicrons receive apo E (for liver recognition) and apo C-II (for activation of lipoprotein lipase).
The TAGs in chylomicrons are cleaved by lipoprotien lipase, once activated by apo C-II, predominantly in the capillaries of adipose and muscle tissues. Lipase is attached to the endothelial lumen via heparan sulfate chains. Deficiency of lipoprotien lipase or apo C-II causes Type I Hyperlipoproteinemia, a rare recessive disorder.
Lipoprotein lipase synthesis and lumenal expression is increased by insulin. Heart lipase has a lower Km than adipose lipase, allowing it to access circulating TAGs even when levels are low.
FFAs can directly enter adipose or muscle cells for storage or energy, or can be transported on albumin to other parts of the body. Most cells can oxidize FFAs to produce energy. Adipocytes can reesterify FFAs to produce TAGs.
Liberated glycerol is returned to the liver, where it is almost exclusively used to produce glycerol-3-phosphate, which can enter glycolysis or gluconeogenesis.
Chylomicron remnants - cholesterol esters, phospholipids, and apolipoproteins - are taken up by the liver via recognition of apo E, where they hydrolyzed and recycled. Apo C-II is returned to HDL.
VLDLs are produced in the liver and are composed primarily of TAG, which they deliver to peripheral tissues. VLDLs contain apo B-100 when secreted, but must pick up apo C-II and apo E from circulating HDL. Abetalipoproteinemia is caused by a defect in TAG transfer protein, leaving apo B unable to be loaded with lipid. As a reult, no chylomicrons or VLDLs can form.
As VLDLs pass through the circulation, lipoprotein lipase liberates FFAs and the VLDL becomes denser. apo C-II and E are returned to HDL, while apo B-100 is retained. Remaining TAGs are transferred to HDL in exchange for cholesterol esters.
With these changes, VLDLs become IDLs, or VLDL remnants. These can be taken up through endocytosis using apo E as a ligand, or become LDLs.
Lp(a), is nearly identical to LDL, and when present in large quantities is a risk factor for heart disease. Levels appear to be predominantly
mediated by genetics, though lifestyle is also involved. Lp(a) is similar to plasminogen, and it is possible that it contributes to heart attacks by
by binding to plasminogen activators and slowing down the breakdown of blood clots.