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Sabtu, 01 Juni 2013

How Is Cholesterol Transported Into Human Cells?

Purpose

    Cholesterol, while commonly associated with terrible conditions such as atherosclerosis and heart attacks, is actually an incredibly important molecule. From it our body generates steroid hormones that regulate such functions as our growth and response to stress. Half of this cholesterol is obtained from the foods we eat. Only animals and animal products (including eggs, milk, and cheese) contain cholesterol. The other half is generated by cells all over the body to supply our metabolic needs. Whether eaten or generated, we must somehow transport cholesterol and the closely related triglycerides and free fatty acids into our cells in order to use them for steroid production. The process of cholesterol transport has important implications for the development of medications to treat hypercholesterolemia.

Transport

    First, it is important to understand that cholesterol is a hydrophobic molecule. Hydrophobic (literally "water fearing") means that it does not mix with watery substances very well. If you have ever tried pouring oil on top of a glass of water you have seen this quality in action. The oil separates from the water, given enough time, and refuses to mix. Since your blood is mostly water, transporting cholesterol through your veins and arteries would be unworkable unless it were packaged inside a hydrophilic (or "water loving") transport system. This transport system is known as the lipoprotein. It is basically a sphere with the hydrophobic molecules on the inside and the hydrophilic molecules on the outside. This structure allows it to pass easily through the bloodstream and protect the hydrophobic molecules within.

    Your intestinal cells work to absorb the cholesterol in your diet and package it into a chylomicron, one type of lipoprotein. This travels through the blood to your liver, which packages the cholesterol into other types of lipoproteins (you may have heard of Low Density Lipoprotein or LDL and High Density Lipoprotein or HDL) and sends them out to all the tissues in your body.

    LDL's job is to carry cholesterol to various cells throughout the body. These cells possess receptors for LDL, specialized molecules on the surface of the cell that catch the LDL as it passes and transport it inside. Once inside, the machinery of the cell begins converting the cholesterol to steroids or, alternately, changing it into a form useful for generating energy (this is the form most associated with the disease atherosclerosis).

    HDL, on the other hand, primarily goes out to retrieve cholesterol from the tissues and return it to the liver. Once there, the liver either uses it to generate necessary materials or mixes the cholesterol with bile and discards it into the intestines as waste. In this way, HDL can help lower total body cholesterol levels.

Implications

    You may have noticed several possible mechanisms by which medications can help lower cholesterol levels. One of these is by preventing production of cholesterol in the body, and this is the function of the most popular class of cholesterol-lowering drugs: the statins (such as simvastatin).
    Another is by preventing dietary absorption of cholesterol. Cholestyramine is an example of a drug that binds digested cholesterol before it can be absorbed by the intestines, forcing it to be passed out with the feces. A newer drug called ezetimibe directly blocks a transport protein in the small intestine, stopping the cell from absorbing the dietary cholesterol. Finally, niacin is a popular drug that indirectly increases HDL levels in the blood by preventing the delivery of various cholesterols and lipoproteins to the liver. The liver responds by generating more HDL, which is sent out to scavenge more cholesterol. In this way, total body cholesterol is reduced.

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