Classification and formation
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There are four major classes of circulating lipoproteins, each with its own characteristic protein and lipid composition. They are chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Within all these classes of complexes, the various molecular components are not chemically linked to each other but are simply associated in such a way as to minimize hydrophobic contacts with water. The most distinguishing feature of each class is the relative amounts of lipid and protein. Because the lipid and protein composition is reflected in the density of each lipoprotein (lipid molecules being less dense than proteins), density, an easily measured attribute, forms the operational basis of defining the lipoprotein classes. Measuring density also provides the basis of separating and purifying lipoproteins from plasma for study and diagnosis. The table gives a summary of the characteristics of the lipoprotein classes and shows the correlation between composition and density.
| Human plasma lipoproteins | |||||
|---|---|---|---|---|---|
| Source: From Christopher K. Mathews, K.E. van Holde, and Kevin G. Ahern, Biochemistry, 3rd ed. (2000), Table 18.1. | |||||
| chylomicron | VLDL | IDL | LDL | HDL | |
| Density (g/ml) | <0.95 | 0.950–1.006 | 1.006–1.019 | 1.019–1.063 | 1.063–1.210 |
| Components (% dry weight) | |||||
| protein | 2 | 7 | 15 | 20 | 40–55 |
| triglycerides | 83 | 50 | 31 | 10 | 8 |
| free cholesterol | 2 | 7 | 7 | 8 | 4 |
| cholesteryl esters | 3 | 12 | 23 | 42 | 12–20 |
| phospholipids | 7 | 20 | 22 | 22 | 22 |
| Apoprotein composition |
A-I, A-II, B-48, C-I, C-II, C-III |
B-100, C-I, C-II, C-III, E |
B-100, C-I, C-II, C-III, E |
B-100 |
A-I, A-II, C-I, C-II, C-III, D, E |
The principal lipid components are triglycerides, cholesterol, cholesteryl esters, and phospholipids. The hydrophobic core of the particle is formed by the triglycerides and cholesteryl esters. The fatty acyl chains of these components are unsaturated, and so the core structure is liquid at body temperature. The table gives more details about the nine different protein components, called apoproteins, of the lipoprotein classes. With the exception of LDL, which contains only one type of apoprotein, all classes have multiple apoprotein components. All the apoproteins, like phospholipids, are amphipathic and interact favorably with both lipids and water. A more-detailed consideration of the character and functions of these lipoprotein particles follows.
| Human plasma apolipoproteins | |||
|---|---|---|---|
| Source: From Dennis E. Vance and Jean E. Vance, Biochemistry of Lipids and Membranes (1985), Table 13.4. | |||
| apolipoprotein | molecular weight | lipoprotein distribution | |
| apoA-I | 28,331 | HDL | |
| apoA-II | 17,380 | HDL | |
| apoB-48 | 241,000 | chylomicrons | |
| apoB-100 | 500,000 | VLDL, LDL | |
| apoC-I | 7,000 | HDL, VLDL | |
| apoC-II | 8,837 | chylomicrons, VLDL, HDL | |
| apoC-III | 8,750 | chylomicrons, VLDL, HDL | |
| apoD | 33,000 | HDL | |
| apoE | 34,145 | chylomicrons, VLDL, HDL | |
Chylomicrons
Chylomicrons are the largest lipoproteins, with diameters of 75–600 nm (1 nm = 10−9 meter). They have the lowest protein-to-lipid ratio (being about 90 percent lipid) and therefore the lowest density. Chylomicrons are synthesized by the absorptive cells of the intestinal lining and are secreted by these cells into the lymphatic system, which joins the blood circulation at the subclavian vein. The triglyceride, cholesteryl ester, and free cholesterol content of these particles is derived from the digestion of dietary fat. Their primary destinations in peripheral areas are heart muscle, skeletal muscle, adipose tissue, and lactating mammary tissue. The transfer of triglycerides and cholesteryl esters to the tissues depletes the lipid-protein aggregates of these substances and leaves remnant chylomicrons, which are eventually taken up by the liver. The lipid and protein remnants are used to form VLDL and LDL, described below.
Very low-density lipoproteins (VLDL)
VLDL is a lipoprotein class synthesized by the liver that is analogous to the chylomicrons secreted by the intestine. Its purpose is also to deliver triglycerides, cholesteryl esters, and cholesterol to peripheral tissues. VLDL is largely depleted of its triglyceride content in these tissues and gives rise to an intermediate-density lipoprotein (IDL) remnant, which is returned to the liver in the bloodstream. As might be expected (see table), the same proteins are present in both VLDL and IDL.
Low-density lipoproteins (LDL)
Low-density lipoproteins are derived from VLDL and IDL in the plasma and contain a large amount of cholesterol and cholesteryl esters. Their principal role is to deliver these two forms of cholesterol to peripheral tissues. Almost two-thirds of the cholesterol and its esters found in plasma (blood free of red and white cells) is associated with LDL.
High-density lipoproteins (HDL)
Lipoproteins of this class are the smallest, with a diameter of 10.8 nm and the highest protein-to-lipid ratio. The resulting high density gives this class its name. HDL plays a primary role in the removal of excess cholesterol from cells and returning it to the liver, where it is metabolized to bile acids and salts that are eventually eliminated through the intestine. LDL and HDL together are the major factors in maintaining the cholesterol balance of the body. Because of the high correlation between blood cholesterol levels and atherosclerosis, high ratios of HDL to cholesterol (principally as found in LDL) correlate well with a lower incidence of this disease in humans.