- Chylomicrons -> the largest size and lowest density
- Very Low Density Lipoproteins (VLDL)
- Intermediate Density Lipoproteins (IDL)
- Low Density Lipoproteins (LDL)
- High Density Lipoproteins (HDL)
| Cholesterol | LDL | HDL | Taking Care | Equation | Table | Index |
Cholesterol is manufactured by the liver. It is an important constituent of cell membranes and the precursor of steroid hormones and bile acids. It is also necessary for repairing cell membranes and manufacturing vitamin D on the skin's surface. Although it is an essential component of life, it has been associated with the two leading causes of death in the world, heart attack and stroke. High cholesterol levels increase the risk of heart attack 2.4 times. Coronary heart disease produces about 600,000 deaths annually. If the cholesterol balance is well maintained between the biosynthesis, utilization, and transportation, its harmful deposition can be retained. Cholesterol and other substances such as trigylcerides are transported in the blood vessels in sphere-shaped body called lipoproteins.
The lipoproteins are made up of five types according to size
Click here for the diagram of a model of cholesterol transport in humans.
The
low density lipoproteins (LDL) is usually known as the "bad"
cholesterol. It transports about 75% of the blood's cholesterol to the
cells. LDL is usually harmless but does have dangerous interactions with
the free radicals on the walls of the artery. These interactions increase
when the body is exposed to environmental toxins, such as cigarette smoke.
These free radicals oxidize the LDL and modify its form. The modified form
of LDL triggers white blood cell in the immune system to gather at
the site, forming a fatty substance called plaque and causing inflammation.
The plaques will gradually built up and reduces blood flow-atherosclerosis-and
contribute to the development of coronary heart disease and stroke. If
blockage occurs, caused by either the gradual formation of plaques or the
rapid formation of a blood clot, the result is a heart attack or a stroke.
The high density lipoprotein serves to remove cholesterol from the walls of the arteries. Thus, the higher level of HDL is usually better.
The total cholesterol level is made up of Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), and triglycerides. Triglycerides are fats in the blood that increase and decrease depending on the diet. It has been suggested that triglycerides is a potential villain. People with low levels of HDL and high triglycerids appear to have a high risk for coronary heart disease and atherosclerosis. Studies suggest that anyone who began taking cholesterol-lowering drugs at a younger age should continue to take them.
The body acquires some cholesterol through diet, but about two-thirds of the total cholesterol is manufactured in the liver cell.
The major stages of cholesterol biosynthesis are
| Acetate -> Isoprenoid intermediate -> squalene -> cyclization product -> Cholesterol |
Acetyl-CoA is converted to isoprene units by a serie of reaction that begins with the formation of hydroxymethylglutaryl-CoA (HMG-CoA). HMG-CoA synthesis requires the participation of two enzymes: thiolate and HMG-CoA synthase. HMG-CoA is the precursor of two isoprenoid intermediates, isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The product, isopentenyl pyrophosphate, undergoes series of reactions to convert to squalene, 2,3-oxidosqualene, and lanosterol. Finally, lanosterol is converted to cholesterol by a nineteen-step mechanism.
Click here for the diagram of the formation of isopentenyl pyrophosphate from HMG-CoA.
HMG-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis. It is multivalently controlled by long-term and short-term processes. The main way HMG-CoA is controlled is by long-term feedback control of the amount of enzyme present in the cell. The short-term control is explained by the fact that the HMG-CoA reductase exists in interconvertible more active and less active forms. This control is exerted to conserve energy when ATP levels fall and AMP levels rise, by inhibiting the biosynthetic pathways.
The pharmacology science imitates the body's control of the cholesterol biosynthesis and invent cholesterol-lowering drugs such as lovastatin to help patient with hypercholesterolemia. The mechanism that the present-day cholesterol-lowering drugs focus on is the NADPH-dependent catalization of HMG-CoA reductase with HMG-CoA to synthesize mevalonate which is eventually converted to isopentenyl pyrophosphate.
The
first step to control cholesterol and triglyceride levels is by maintaining
a healthy diet. The diet should be low in unsaturated fat, saturated fat,
protein and cholesterol. Cholesterol is found only in animal tissues: meat,
dairy products, egg yolks, and shellfish. The total cholesterol intake
in a day should not exceed 300 mg. It is best to eat skinless chicken and
fish rather than pork or beef. Skim milk and egg whites are good substitutes.
Vitamin E may help LDL cholesterol to resist the oxidation interaction
with the free radicals on the walls of the artery.
Cigarette
smoking is responsible for approximately 20% of all deaths from heart disease.
It lowers HDL-cholesterol levels. 
cholesterol
levels and heart disease should use drug therapy as soon as possible. Some
patients with high cholesterol levels are treated with drug therapy even
when there are no symptoms of heart disease. There are several cholesterol-lowering
drugs in the market. 
