Cholesterol is a white, waxy, fatlike substance that occurs in the tissues of all vertebrates, and is found, in association with other sterols, throughout the animal kingdom; it seldom occurs in significant amounts in higher plants. It is the best- known member of the sterols (see sterol), a biologically important group of lipid alcohols. Excess cholesterol can build up in the bloodstream and accumulate on the walls of arteries, forming "plaques," which can clog the blood vessels and lead to heart attacks and strokes. Because of its role in heart disease in humans, cholesterol has been the focus of much debate over what constitutes healthy or unhealthy levels of cholesterol in the blood and how to reduce cholesterol in the diet.
In higher animals cholesterol has a number of functions. It is a structural component of cell membranes. The cholesterol content of a membrane varies with the tissue and with specific membrane function. The ratio of cholesterol to polar lipids (phospholipids and glycolipids) affects the stability, permeability, and protein mobility of a membrane. Membranes with high ratios have high stability and relatively low permeability; their major function is a protective barrier. Membranes of intracellular organelles such as mitochondria have low cholesterol ratios and are consequently fluid and permeable. They serve primarily in synthetic and degradative reactions and in energy production. The outer membranes of most cells have intermediate cholesterol-polar lipid ratios and have both protective and metabolite-transport functions.
In addition to its role in membrane structure cholesterol has other important functions. Cholesterol is stored in the adrenals, testes, and ovaries, chiefly as the fatty acid ester, and converted to steroid hormones. These hormones include the male and female sex hormones (androgens and estrogens) as well as the adrenal corticoids (cortisol, corticosterone, aldosterone, and others). In the liver cholesterol is the precursor of the bile acids, 24 steroid carboxylic acids that aid in the digestion of foods, especially lipids, and, when linked with the amino acids glycine or taurine, form the bile salts.
In the average American adult, the total amount of lipoprotein- bound cholesterol circulating in the blood is about 200 mg per 100 ml of serum. Cholesterol is obtained from foods having saturated fatty acids (see fatty acid) and is also synthesized from acetate, primarily in the liver. Normally the total amount of cholesterol from these two sources remains constant because the rate of cholesterol synthesis in the liver is under feedback control. When the dietary intake is high, liver synthesis is low; when intake is low, synthesis increases.
Dietary cholesterol is transported in the blood from the intestine to the liver by means of large lipoprotein molecules. The liver then secretes Very Low Density Lipoprotein (VLDL)-- containing cholesterol and cholesterol ester among other compounds--into the blood. VLDL is partially converted in adipose tissue (fat) to Low Density Lipoprotein (LDL). LDL is the major transport protein for cholesterol, supplying both free and esterified cholesterol to body tissues. High Density Lipoprotein (HDL) is involved in the transport of cholesterol to the liver to be broken down and excreted, and in removing some LDL cholesterol from artery walls.
If a person's intake of dietary fat is high, many experts consider that levels of serum cholesterol will also increase, causing greater risk of heart disease and especially atherosclerosis. Studies have shown that high levels of HDL cholesterol reduce that risk, and high levels in other lipoproteins, particularly LDL, have the opposite effect. A 1984 report indicated that reduction of LDL ratios would lower the risk of heart disease, and a 1987 report provided evidence that reduction of cholesterol could have a positive effect in some persons with high cholesterol levels. Various drugs can help lower cholesterol levels for persons with very high cholesterol levels. Studies recommend that adults try to limit their cholesterol intake, to reduce the risk of coronary disease. Controversy has surrounded the suggestion that mass screening for high cholesterol levels should begin in childhood.