Structure And Classification Of Lipoproteins And Apolipoproteins
Although cholesterol and TG serve several important functions within the body, they are insoluble particles and must be packaged into lipoproteins in order to circulate in the plasma, from sites of synthesis or absorption to sites of use. The core of the lipoprotein, containing cholesterol ester and TG, is nonpolar and hydrophobic, and the outer layer of the lipoprotein particle , is polarized, permitting the lipoprotein particles to be transported in the circulation. Apolipoproteins such as apoB, apoC and apoE, coat lipoprotein particles and serve a number of functions including the transport of lipids in the blood and recognition of lipoprotein particles by enzymes which process or remove lipids from the lipoprotein particles. For example, apoC-II activates the enzyme lipoprotein lipase , which removes TG from lipoprotein particles such as chylomicrons and VLDL.
VLDL is a lipoprotein particle similar to chylomicrons, which contains a high concentration of TG. VLDL is synthesized from free-fatty acids formed in the catabolism of chylomicrons in the liver, or from endogenous production of TG. The TG component of VLDL also undergoes hydrolysis by capillary LPL to provide fatty acids to adipose and muscle tissue. The remaining lipid portion is called IDL. IDL is then converted to LDL by enzymatic action of hepatic lipase or is taken up by the liver via the LDL receptor.
What Are Hdl And Ldl
HDL and LDL are two types of lipoproteins.They are a combination of fat and protein. The lipids need to be attached to the proteins so they can move through the blood. HDL and LDL have different purposes:
- HDL stands for high-density lipoproteins. It is sometimes called the “good” cholesterol because it carries cholesterol from other parts of your body back to your liver. Your liver then removes the cholesterol from your body.
- LDL stands for low-density lipoproteins. It is sometimes called the “bad” cholesterol because a high LDL level leads to a buildup of cholesterol in your arteries.
Measuring Hdl Concentration And Sizes
As technology has reduced costs and clinical trials have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations and size at lower costs have become more widely available and increasingly regarded as important for assessing individual risk for progressive arterial disease and treatment methods.
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The Discovery Of Plasma Lipoproteins
In 1929, Michel Macheboeuf, working at the Pasteur Institute in Paris, reported the isolation from horse serum of a stable, water-soluble lipoprotein that could be precipitated from a neutral 50% saturated ammonium sulfate extract of serum by lowering the pH to 3.8. This lipoprotein contained 59% protein and 41% lipid, which consisted of 18% cholesterol and 23% phospholipid and could be redissolved in water to form a clear solution. Later on it was shown that this lipoprotein was an -globulin and had the same composition as the -lipoprotein that we now recognize as HDL .
In 1941, Blix et al., in Upsala, observed upon electrophoresis of plasma that significant amounts of lipid were associated with both the – and -globulins. In 1947, in the same Swedish laboratory, Pederson was able to flotate a -lipoprotein in the ultracentrifuge at the density of 45% saturated magnesium sulfate.
Another lipoprotein, Lp, was discovered by Kare in Norway in a immunochemical study designed to detect antigenic variations in human LDL. Lp is a complex particle in human plasma that is assembled from one LDL molecule that carries all the lipid and one glycoprotein , which has a high degree of homology to plasminogen. Lp provides some risk for atherosclerosis.
What Treatments Are Available For High Cholesterol
Medical treatment may include:
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Changing risk factors. Some risk factors that can be changed include lack of exercise and poor eating habits.
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Cholesterol-lowering medicines. Medicines are used to lower fats in the blood, particularly LDL cholesterol. Statins are a group of medicines that can do this. They include simvastatin, atorvastatin, and pravastatin. Two other types of medicines that lower cholesterol levels are bile acid sequestrants such as colesevelam, cholestyramine, and colestipol, and nicotinic acid .
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Estimating Hdl Via Associated Cholesterol
Clinical laboratories formerly measured HDL cholesterol by separating other lipoprotein fractions using either ultracentrifugation or chemical precipitation with divalent ions such as Mg2+, then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The reference method still uses a combination of these techniques. Most laboratories now use automated homogeneous analytical methods in which lipoproteins containing apo B are blocked using antibodies to apo B, then a colorimetric enzyme reaction measures cholesterol in the non-blocked HDL particles.HPLC can also be used. Subfractions can be measured, but clinical significance of these subfractions has not been determined. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate.
| High HDL level, optimal condition considered correlated against heart disease |
High LDL with low HDL level is an additional risk factor for cardiovascular disease.
How Can I Raise My Hdl Level
If your HDL level is too low, lifestyle changes may help. These changes may also help prevent other diseases, and make you feel better overall:
- Eat a healthy diet. To raise your HDL level, you need to eat good fats instead of bad fats. This means limiting saturated fats, which include full-fat milk and cheese, high-fat meats like sausage and bacon, and foods made with butter, lard, and shortening. You should also avoid trans fats, which may be in some margarines, fried foods, and processed foods like baked goods. Instead, eat unsaturated fats, which are found in avocado, vegetable oils like olive oil, and nuts. Limit carbohydrates, especially sugar. Also try to eat more foods naturally high in fiber, such as oatmeal and beans.
- Stay at a healthy weight. You can boost your HDL level by losing weight, especially if you have lots of fat around your waist.
- Exercise. Getting regular exercise can raise your HDL level, as well as lower your LDL. You should try to do 30 minutes of moderate to vigorous aerobic exercise on most, if not all, days.
- Avoid cigarettes.Smoking and exposure to secondhand smoke can lower your HDL level. If you are a smoker, ask your health care provider for help in finding the best way for you to quit. You should also try to avoid secondhand smoke.
- Limit alcohol. Moderate alcohol may lower your HDL level, although more studies are needed to confirm that. What we do know is that too much alcohol can make you gain weight, and that lowers your HDL level.
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How Do I Know What My Hdl Level Is
A blood test can measure your cholesterol levels, including HDL. When and how often you should get this test depends on your age, risk factors, and family history. The general recommendations are:
For people who are age 19 or younger:
- The first test should be between ages 9 to 11
- Children should have the test again every 5 years
- Some children may have this test starting at age 2 if there is a family history of high blood cholesterol, heart attack, or stroke
For people who are age 20 or older:
- Younger adults should have the test every 5 years
- Men ages 45 to 65 and women ages 55 to 65 should have it every 1 to 2 years
Class B Scavenger Receptor B1
SR-B1 is expressed in the liver, adrenal glands, ovaries, testes, macrophages, and other cells. In the liver and steroid producing cells, it mediates the selective uptake of cholesterol esters from HDL particles. In macrophages and other cells, it facilitates the efflux of cholesterol from the cell to HDL particles.
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Classification Density And Composition Of Lipoproteins
There are five types of lipoproteins. Among these, the three major ones are LDL, HDL, and VLDL. The values of each of these lipoproteins in the blood plasma are measured by a blood test known as the lipid profile or lipid panel.
The most common way lipoproteins are classified is according to the density of the apolipoproteins or less commonly by weight per unit volume.
The four lipoprotein fractions, in order of increasing density, are
Chylomicrons
Low-density lipoprotein , and
High-density lipoprotein
LDL and HDL contain the least amount of triglycerides and relatively more amounts of cholesterol and protein.
Lipoprotein particles vary in size from 10 to 1000 nanometers. Even the density of the lipoproteins differs. Generally, more the density of the lipoproteins smaller is the size of the lipoprotein particle. Again, as a general rule, lipoproteins with a higher fat to protein ratio are larger and less dense.
The sizes and the type of lipoprotein are distinguished by the processes of lipoprotein electrophoresis and ultracentrifugation. This test determines the abnormal distribution and concentration of lipoproteins in the serum, which is a potential risk factor in the development of coronary artery disease
The Role Of Receptor Mediated Events In Fat Transport
Knowledge of the importance of lipoprotein receptors, which feature protein-protein interactions in the clearance of circulating lipoproteins, has modernized views of fat transport the pathways are shown in . As noted earlier, chylomicrons arise in the gut during fat digestion, enter the thoracic duct and then the blood stream where they are attacked by LPL, which reduces their triglyceride content by 75% and produces a chylomicron remnant that is taken up by B-100-E receptors on hepatocytes. Within the liver, the chylomicron remnant is decomposed to its amino acids and component lipids. Cholesterol released from lysosomes in hepatocytes can be excreted into bile, converted into bile acids, incorporated into VLDL for secretion into the blood via the Golgi apparatus or esterified with long-chain fatty acids and stored in the hepatocyte.
Receptor-mediated pathways of lipoprotein metabolism. Three major pathways are involved: chylomicrons, VLDL and HDL. Intermediate density lipoprotein is the remnant of VLDL and is cleared by the liver. LDL, which contains only apolipoprotein B-100, is the final product of the pathway most of it is returned to the liver. Some LDL is taken up by extrahepatic LDL receptors and some by a scavenger pathway. The apopeptides contained in each lipoprotein are indicated. Three plasma enzymes essential for lipoprotein metabolism include LPL , LCAT and HTGL
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The Characterization Of The Lipoprotein Apopeptides
Attempts were then made to identify the protein components of the major lipoproteins . They were delipidated with organic solvents and the resulting peptides fractionated and studied to determine their size, shape and amino acid composition. At first, there were difficulties from the insolubility of some of the peptides and the denaturation and/or proteolysis of others during isolation. Nonetheless, by the mid-1970s, it became clear that there were four families of peptides associated with the major lipoproteins. The A-apopeptides were associated primarily with the -lipoproteins the B-apopeptides with -lipoproteins and chylomicrons the migratory C-apopeptides with all lipoproteins except LDL and the E-apopeptide with VLDL, intermediate density lipoprotein and HDL . Most lipoprotein apopeptides are synthesized in the liver or the intestine, but one, apolipoprotein redundant E, is synthesized in all cells, except the gut.
Of particular importance for lipoprotein clearance are apo B-100 and apo E. Apo B-100, with 4536 amino acids and a molecular weight of 550 kDa is the largest protein known in mammals. Apo B-48, the form of apo B present in chylomicrons, is formed in the intestine from the same gene by mRNA editing. The mRNA for apo B-100 is truncated at residue 2152 to produce a smaller apo B devoid of its binding site to the LDL receptor.
Lipid And Lipoprotein Metabolism
Lipids = cholesterol and triglyceride – are insoluble in plasma and are transported in lipoproteins.
Functions = energy utilization, steroid hormone production, bile acid production, lipid deposition.
Lipoprotein consists of esterified and unesterified cholesterol, triglycerides, phospholipids and apolipoproteins. The proteins function as cofactors and ligands for receptors.
Major lipoproteins include:
Exogenous pathway for lipid metabolism:
Endogenous pathway for lipid metabolism:
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A Rudimentary View Of Fat Transport
In the 1960s, a more coherent view of fat transport began to emerge, aided by extensive reviews of a large body of evidence by and . On the basis of physiologic studies of organ function and isotopic studies of lipoprotein turnover, it was concluded that triglycerides are transported by chylomicrons from the gut to adipose tissue, and by VLDL from the liver to adipose tissue. Both processes require lipoprotein lipase and the local uptake of FFA by fat cells. were the first to demonstrate a brisk turnover of adipose tissue lipid in mice fed deuterium-labeled precursors. It was then shown by study of A-V differences that fat transport from adipose tissue to liver and other tissues was accomplished by FFA bound to albumin. Isotopic studies showed that the turnover time of FFA in humans is about 3 min, which means that about 200 g of fatty acids is transported by human plasma each 24 h. . Because the labeled FFA contributed < 50% of the respiratory CO2 over 24 h, it appeared that extensive recycling of FFA must occur.
Only About 20% Of The Cholesterol In Your Bloodstream Comes From The Food You Eat Your Body Makes The Rest
Cholesterol has a bad reputation, thanks to its well-known role in promoting heart disease. Excess cholesterol in the bloodstream is a key contributor to artery-clogging plaque, which can accumulate and set the stage for a heart attack. However, the role of cholesterol in your body is not all negative.
To fully explain cholesterol, you need to realize that it’s also vital to your health and well-being. Although we measure cholesterol production in the blood, it’s found in every cell in the body. The Harvard Special Health Report Managing Your Cholesterol explains cholesterol as a waxy, whitish-yellow fat and a crucial building block in cell membranes. Cholesterol also is needed to make vitamin D, hormones , and fat-dissolving bile acids. In fact, cholesterol production is so important that your liver and intestines make about 80% of the cholesterol you need to stay healthy. Only about 20% comes from the foods you eat.
If you eat only 200 to 300 milligrams of cholesterol a day , your liver will produce an additional 800 milligrams per day from raw materials such as fat, sugars, and proteins.
Since cholesterol is a fat, it can’t travel alone in the bloodstream. It would end up as useless globs . To get around this problem, the body packages cholesterol and other lipids into minuscule protein-covered particles that mix easily with blood. These tiny particles, called lipoproteins , move cholesterol and other fats throughout the body.
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Lipoproteinsgood Cholesterol Bad Cholesterol
Cholesterol is an essential structural component of cell membranes and of the myelin sheathsthat insulate the axons of nerve cells. Cholesterol is also a precursor of steroid hormonesand of the bile acids necessary for digestion. The liver produces approximately 70% of the cholesterol used by the body, and the other 30% comes from the diet.
Lipoproteins are small spherules that transport fats in the body and consist of protein, cholesterol, triglycerides, and phospholipids. The terms “good” and “bad” cholesterol refer to High Density Lipoproteins and Low Density Lipoproteins , respectively.High levels of LDL are associated with coronary atherosclerosis, whereas high levels of HDLappear to protect against cardiovascular diseases.
There are five main classes of lipoproteins:
- Chylomicrons
- Very Low Density Lipoproteins
- Intermediate Density Lipoproteins
- Low Density Lipoproteins
- High Density Lipoproteins
Lipoprotein particles range in size from 10 to 1000 nanometers. The largest lipoproteins are about one tenth the size of a red blood cell.The density of lipoproteins increases in proportion to their ratio of proteins to lipids.In general, as the density of a lipoproteins increases, the size of the particles decreases.The outer layer of a lipoprotein consists of a water-soluble layer ofapolipoproteins, phospholipids and cholesterol. The center of a lipoprotein is composedof cholesteryl esters, triglycerides, fatty acids and fat-soluble vitamins like Vitamin E.
Where Is Cholesterol Made
Some of our cholesterol comes from the food we eat, but most is made in the liver in a complex 37-step process.
Cholesterol and another type of blood fat called triglycerides cannot circulate loosely in the blood, so the liver packages them into parcels called lipoproteins.
The lipoproteins are then released into the blood and carried around the body to wherever they’re needed.
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What Is A Healthy Blood Cholesterol Level
High blood cholesterol is a significant risk factor for heart disease and stroke. You can lower your risk by getting more exercise, losing weight if you are overweight, quitting smoking, and eating a healthy diet. But blood cholesterol is very specific to each person. Your healthcare provider will determine your total cholesterol and LDL goals based on other risk factors. For that reason, a full lipid profile is an important part of your health history and important information for your healthcare provider to have.