Cholesterol in The Body

Cholesterol belongs to the class of chemicals known as lipids, or fats. If you held an ounce of cholesterol in your hand, you would see a waxy powder that resembles very fine scrapings from a candle with a whitish-yellow tinge. Animals like us need cholesterol and other lipids for many things. Lipids provide some of the chemical energy that fuels cells. Cholesterol is a building block of cell membranes, the critically important "skin" that surrounds cells. It is used to make the bile acids that help us digest and absorb food. Cholesterol is also an important precursor to vitamin D and a number of hormones, including testosterone and estrogen. In fact, cholesterol is so important for our proper functioning that our bodies regulate its level in the blood — called serum cholesterol or blood cholesterol — fairly tightly. The body does so by producing cholesterol on its own when diet alone does not supply enough. Nutritionists use the words "dietary cholesterol" to distinguish the kind you eat from the kind your body manufactures.

An adult who eats only 200–300 milligrams (mg) of cholesterol a day (one egg yolk has about 200 mg) will make an additional 800 mg a day, most of it in the liver and some in the intestine. So even if you were able to eliminate every morsel of cholesterol from your diet, your liver would make enough to supply your body's needs, assembling cholesterol from raw materials such as fats, sugars, or proteins.

HDLs, LDLs, and Other Fat Particles

The bloodstream is the distribution channel for delivering a steady supply of cholesterol and other lipids to cells from your brain to your toes. This process isn't as simple as it sounds. Like oil and water, lipids and blood don't mix. If your liver or intestine simply dumped lipids into your blood, they would congeal into unusable globs. To get around this problem, the body packages fat into minuscule protein-covered particles that mix easily with blood and flow with it (see Figure 1). These tiny particles are called lipoproteins ("lipid" plus "protein"), while the proteins themselves are called apolipoproteins ("apo" means "away," indicating the proteins that are left behind once the lipids are removed). Cholesterol helps stabilize lipoprotein particles, much as the cholesterol in egg yolk stabilizes mayonnaise.

Figure 1: The particles story   The particles story   Four kinds of fat-containing particles known as lipoproteins circulate in the bloodstream. The smallest and densest are the high-density lipoproteins (HDLs, left), which contain more protein than fat (cholesterol and triglycerides). The largest and lowest-density particles are the chylomicrons (far right), which contain more fat (mostly triglycerides).

Like a highway at rush hour, your bloodstream carries many sizes of fat-transporting particles, from small, dense ones to light, fluffy ones. Lipoproteins are generally classified according to the balance of fat and protein they contain. The higher the ratio of fat to protein, the lower the lipoprotein particle density — that is, more fat means lower density. The various classes of lipoproteins also differ in the types of proteins they contain. Not only does this structure provide a protective wrapping for the fat, but it also acts like an address label that helps the body route fat-filled particles to specific destinations.

With regard to heart disease, the most important lipoproteins are high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL). These were all discovered in the late 1940s. A type of lipoprotein discovered earlier was given a Greek name, chylomicron (pronounced ky-lo-MI-kron), meaning "particle of digestive liquid." If the chylomicron had been discovered later it would probably have been called something like "extremely low-density lipoprotein," because it carries so much fat in relation to its protein content.

Much of the noncholesterol fat found in lipoprotein particles is triglyceride. Triglycerides make up most of the fat that you eat and most of the fat that circulates in your bloodstream. The name comes from the structure — three fatty acids bound to an alcohol called glycerol. Triglycerides are essential for good health because your tissues rely on them for energy. But as with that other essential molecule, cholesterol, too much triglyceride seems to be bad for the arteries and the heart.

Traveling in the fat lane

As you eat, your intestine absorbs fat from food. Intestinal enzymes rapidly dismantle the long, complex fat molecules into their component fatty acids, reassemble them into new triglyceride molecules, and package these — along with a small amount of cholesterol — into chylomicrons (see Figure 2). The amount of triglyceride-rich particles in the blood increases for several hours after a meal, as the intestine releases a barrage of chylomicrons filled with triglycerides. That is why you're asked to fast before going in for a cholesterol test that measures the different lipids in your blood. If you don't, the triglyceride amounts appear higher than usual, which skews the readings of the other lipids as well (see "The blood test" for more on cholesterol testing).

Figure 2: How food becomes cholesterol   How food becomes cholesterol

At the same time, dietary carbohydrates and proteins that are absorbed from the intestine pass to the liver, which converts them to triglyceride molecules, packages them with apolipoproteins and cholesterol, and releases the resulting VLDLs into the bloodstream (see Figure 3). As chylomicrons and VLDLs course around the body, they temporarily stick to the walls of blood vessels in muscle tissue that needs energy or in fatty tissue (adipose tissue) that stores energy. Enzymes come along and remove most of their load of triglyceride molecules, which are then transported inside the muscle or fat cells. As triglyceride is drained from the chylomicron or VLDL particles, their protective protein coats are rearranged and reconfigured, essentially giving them a new address label that can be read by the liver or other tissues that take up lipoproteins.

The creation of LDL. Both chylomicrons and VLDLs become smaller and denser as they give up their low-density fatty cargo. Eventually, all that remains is the packaging material — the protein and cholesterol — and a fraction of the original triglyceride. Chylomicron remnants don't linger in the circulation; the liver filters them from the system and recycles their components. Many of the triglyceride-depleted VLDL remnants, though, keep circulating and undergo further modification of their lipid and protein content. Eventually these particles are converted to LDL, a lipoprotein that carries most of the total blood cholesterol in association with a single apolipoprotein, called apolipoprotein B (apo B for short).

Virtually all cells in the body can take up and use LDL for their individual cholesterol needs. But because there are usually more LDL particles in circulation at any one time than your body can use, it's your liver's job to clear the excess from the blood and use it to make more bile acids or new lipoproteins. If the liver can't keep up with the supply of LDL, these particles can come to rest in the wrong places, typically in the lining of blood vessels. In extreme cases, they may settle in the skin and tendons, where they form yellow deposits called xanthomas or, if they appear on the eyelids, xanthelasmas. Both terms come from a Greek term for a yellow plate.

HDL in the bloodstream. HDL, the "good" cholesterol made by the liver and intestines, resembles LDL only in its acronym. It looks and behaves quite differently from LDL. HDL particles, by definition, have lots of protein but not much fat. They have two main jobs. HDL particles give chylomicrons and VLDLs the proteins that signal the liver to trap them and extract their fat. They also sponge up excess cholesterol from the linings of blood vessels and elsewhere and carry it off to the liver for disposal (see Figure 3). If you think of the LDL that builds up inside blood vessels as circulatory garbage, then HDL is like a garbage collector that picks up fatty materials from blood vessel walls and delivers them to the liver for removal. And studies suggest that HDL may even have a third function: to absorb and inactivate inflammatory molecules in LDLs that can damage artery walls.

Figure 3: Give and take: Cholesterol in the bloodstream   Give and take: Cholesterol in the bloodstream   The liver releases fat-laden VLDLs into the bloodstream. VLDLs send some of their fatty triglycerides into the body's muscles and fat tissues, and the VLDLs become cholesterol-rich LDLs. The body needs LDLs for many functions, but often there are more LDLs than the body needs. If so, they are deposited in the lining of blood vessels in the form of cholesterol-rich plaque, which can cause heart disease. HDLs are the garbage collectors, scooping up the cholesterol and carrying it back to the liver for disposal.