Structure and Functions (Magill’s Medical Guide, Sixth Edition)
Living cells are bounded by a cell membrane composed of a double layer of phospholipid, associated with and traversed by proteins that have catalytic, transportation, and signaling functions. Variable amounts of sterol are interspersed among the molecules of phospholipid in each membrane layer. Sterols are essential components in the membranes of fungal, plant, and animal cells (but not in bacteria). In vertebrates, the predominant sterol is cholesterol. There is little or no cholesterol in plant cell membranes; its place is taken by chemically related substances, chiefly sitosterol. This fact is of nutritional significance; only animal products add cholesterol to the diet.
In mammals, cholesterol is the precursor of steroid hormones, which are essential for mineral balance, adjustment of the body to stress, and normal reproductive function. It is also the precursor of bile acids, which are required for the absorption of dietary lipids. Bile acids play a role in cholesterol balance, since their formation and secretion by the liver, along with some free cholesterol, is the only significant pathway for removal of cholesterol from the body.
Cholesterol itself is required for normal functioning of the mammalian cell membrane. Cholesterol alters the membrane’s fluidity—the ease with which proteins embedded in the membrane can move about and interact with one another—and also affects the activity of enzymes and...
(The entire section is 2068 words.)
Disorders and Diseases (Magill’s Medical Guide, Sixth Edition)
Excessive levels of LDL cholesterol are associated with an increased risk of coronary heart disease and stroke. Efforts to reduce LDL cholesterol through changes in diet or through drugs take advantage of what is known about cholesterol balance in individual cells and in the body as a whole. The latter is determined by three factors: the dietary intake of cholesterol, the rate of cholesterol synthesis within the body (principally by the liver), and the rate of cholesterol disposal (also principally by the liver, through secretion of free sterol into the bile and by the conversion of cholesterol to bile acids). Accordingly, levels of LDL cholesterol can be diminished by limiting the intake and synthesis of new cholesterol, reducing cholesterol secretion by the liver (in the form of an LDL precursor particle), promoting LDL uptake by the liver (mediated by the LDL receptor), and increasing the formation and secretion of bile acids and free cholesterol.
The body can meet its need for cholesterol through synthesis; there is no dietary requirement. Cholesterol deficiency does not arise in humans even on a purely vegetarian (cholesterol-free) diet. The average Western diet, rich in meat and dairy products, contains between 250 and 500 milligrams of cholesterol per day. Small amounts of cholesterol in the diet are fairly well absorbed, but efficiency declines with larger quantities; on average, about half of the cholesterol...
(The entire section is 1293 words.)
Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
The average adult body contains about 150 grams of cholesterol. Less than 5 percent of this cholesterol is in circulating lipoproteins or trapped in atherosclerotic lesions. The remainder performs essential functions as a structural component of membranes and as the precursor of other vital substances. Although researchers have learned much about the subcellular distribution, the pathway for biosynthesis, and the mechanisms for transport of cholesterol, important questions remain. It is not known how cholesterol is transported within the cell or what determines its relative distribution among different cellular membranes. It is not known what signals suppress the synthesis of HMG CoA reductase and LDL receptors or how the message is transmitted to the nucleus to diminish transcription of these genes. Some product of mevalonic acid metabolism other than cholesterol also regulates the expression of HMG CoA reductase, but this factor has not yet been identified. It is not known why cholesterol is an absolute requirement for functioning of mammalian cell membranes. It is not known what determines the fraction of dietary cholesterol that is absorbed across the intestinal lining. Finally, there is much to learn about factors that regulate the secretion and reuptake of lipoproteins by the liver and that control the return to the liver of cholesterol in HDL.
These questions are of practical as well as academic interest....
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Dietschy, John M. “Physiology in Medicine: LDL Cholesterol—Its Regulation and Manipulation.” Hospital Practice 25 (June 15, 1990): 67-78. An excellent nontechnical introduction to the subject of cholesterol balance and its regulation, by a major contributor to the field. The article discusses the effect of diet and of drug interventions.
Freeman, Mason W., with Christine Junge. The Harvard Medical School Guide to Lowering Your Cholesterol. New York: McGraw-Hill, 2005. Written for general readers, this book explains, among other topics, the differences between “good” and “bad” cholesterol, discusses cholesterol levels and managing those levels for prime health, and examines the use of cholesterol-lowering prescription drugs.
Grundy, Scott M. Cholesterol and Atherosclerosis. Philadelphia: J. P. Lippincott, 1990. The author provides a general overview of cholesterol balance, elevated plasma cholesterol, and its management by diet and drugs. Although intended for physicians, the book is written in a simple and direct style and is profusely illustrated.
Hirsch, Anita. Good Cholesterol, Bad Cholesterol: An Indispensable Guide to the Facts About Cholesterol. New York: Avalon, 2002. An easy-to-browse format that provides medical facts about cholesterol, lifestyle guidance to managing cholesterol levels, and recipes for low-cholesterol meals.
(The entire section is 330 words.)
Cholesterol (Encyclopedia of Science)
Cholesterol is a waxy substance found in the blood and body tissues of animals. It is an important structural component of animal cell membranes. Cholesterol is a lipid, a group of fats or fatlike compounds that do not dissolve in water. More specifically, it is a type of lipid known as a steroid. Other steroids include hormones, which are chemical substances produced by the body that regulate certain activities of cells or organs.
Cholesterol in the human body
Cholesterol is a biologically important compound in the human body. It is produced by the liver and used in the manufacture of vitamin D, adrenal gland hormones, and sex hormones. Large concentrations of cholesterol are found in the brain, spinal cord, and liver. Gallstones that occur in the gall bladder are largely made up of cholesterol. It is also found in bile (a fluid secreted by the liver), from which it gets its name: chol (Greek for "bile") plus stereos (Greek for "solid").
Normally, cholesterol produced by the liver circulates in the blood and is taken up by the body's cells for their needs. Cholesterol can also be removed from the blood by the liver and secreted in bile into the small intestine. From the intestine, cholesterol is released back into the bloodstream.
The body does not need cholesterol from dietary sources because the liver...
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Cholesterol (Encyclopedia of Alternative Medicine)
Cholesterol is a fatty substance found in animal tissue and is an important component to the human body. It is manufactured in the liver and carried throughout the body in the bloodstream. Problems can occur when too much cholesterol forms an accumulation of plaque on blood vessel walls, which impedes blood flow to the heart and other organs. The highest cholesterol content is found in meat, poultry, shellfish, and dairy products.
Cholesterol is the Dr. Jekyll and Mr. Hyde of medicine, since it has both a good side and bad side. It is necessary to digest fats from food, make hormones, build cell walls, and participate in other processes for maintaining a healthy body. When people talk about cholesterol as a medical problem, they are usually referring to high cholesterol. This can be somewhat misleading, since there are four components to cholesterol. These are:
- LDL, the so-called bad cholesterol
- HDL, the so-called good cholesterol
- triglycerides, a blood fat lipid that increases the risk for heart disease
- total cholesterol
The U.S. Food and Drug Administration (FDA) estimates that 90 million American adults, roughly one-half of the adult population, have elevated cholesterol levels. High...
(The entire section is 2290 words.)
Cholesterol (Encyclopedia of Food & Culture)
CHOLESTEROL. Cholesterol is one of the most widely disseminated organic compounds in the animal kingdom. Almost three hundred years ago, Antonio Vallisnieri observed that gallstones were soluble in turpentine or alcohol. Poulletier de la Salle, some thirty years later, demonstrated that the main constituent of gallstones could be crystallized from alcohol. This substance was thought to be a wax until 1815, when Michel Eugène Chevreul showed that it was not saponifiable and gave it the name "cholesterine" derived from the Greek chole, bile, and steros, solid. Soon thereafter, it was isolated from blood, brain, tumors, and egg yolk. The isolated compounds were shown to be identical. In 1843 Vogel found it in atherosclerotic arteries.
The chemical structure of cholesterol was elucidated over the years beginning in 1859. The compound was shown to contain a secondary hydroxyl group and a double bond. The exact empirical formula (C27H46O) was established in 1888 by Friedrich Reinitzer. Proof of structure was obtained chiefly through the brilliant work of Adolf Windaus and Heinrich Wieland. The structure of cholesterol suggested by Windaus and Wieland in the 1920s was incorrect, but that does not detract in any way from their contribution. The true structure was established in the 1930s based on X-ray diffraction data.
There were many suggestions regarding the biological synthesis of cholesterol. The biosynthetic pathway became accessible with the introduction of radioactive carbon in the 1940s. The biosynthetic scheme was generally elucidated by the work of Konrad Bloch, George Popjak, and John Cornforth. It was first shown that cholesterol could be synthesized in mammals and ergosterol in yeast from small organic molecules. Eventually it was shown that all twenty-seven carbon atoms of cholesterol were derived from the two carbon atoms of acetate. The methyl group of acetate contributed fifteen of the twenty-seven carbons of cholesterol and the carboxyl group contributed twelve. The pathway began with the condensation of two acetate residues to give acetoacetate and addition of one more two-carbon moiety to yield hydroxymethylglutaric acid (HMG). HMG lost a carbon atom and the resulting compound rearranged to provide an isoprene unit. Two five-carbon units combined to give a geranyl derivative that added another isoprene to give a farnesyl unit. Two farnesyl units united to provide squalene (C30H50), a hydrocarbon found in the livers of some species of shark that cyclyzed to yield lanosterol, a thirty-carbon atom sterol also found in sheep wool. In a series of rearrangements and demethylations, lanosterol yielded cholesterol. The key step in this complex synthetic pathway involves the reduction of HMG-CoA. Inhibition of HMG-CoA reductase is the basis of a number of potent new serum cholesterol-lowering drugs.
Cholesterol represents about 0.2 percent of the weight of the human body. As Table 1 shows, the bulk of the body's cholesterol is present in two tissues; one is the brain and nerve tissue, the other is muscle. In the brain, cholesterol is thought to act as an insulator, but there have been relatively few studies of the metabolism of brain cholesterol. The next large reservoir of cholesterol is muscle. Between them, nervous tissue and muscle carry 44 percent of the body's cholesterol. The cholesterol in these reservoirs turns over slowly.
Cholesterol is ubiquitous in the human body, where it plays structural and metabolic roles. Together with phospholipid, cholesterol is present in every cell membrane. In the adrenals, cholesterol is converted to adrenocortical hormones such as cortisone. In the gonads,
|Distribution of cholesterol in a 70-kg man|
|Tissue||Cholesterol content (g)||% of Total|
|Brain, nervous system||32.0||23|
|Connective tissue, body fluids||31.3||22|
|Heart, lungs, kidneys, spleen||5.0||4|
cholesterol is converted to the appropriate sex hormonestradiol in women, testosterone in men. The cholesterol in skin is the precursor of 7-dehydrocholesterol, which is ultimately converted to vitamin D. The major catabolic products of cholesterol are the bile acidsholic and chenodeoxycholic. These are designated as the primary bile acids; they are metabolized in the liver to deoxycholic and lithocholic acids. It has been estimated that over 90 percent of biologically synthesized cholesterol is metabolized to bile acids. In general, the body synthesizes more cholesterol than it ingests.
In 1912 Nicolai Anitschkow showed that cholesterolfed rabbits developed aortic deposits similar to early human atherosclerosis. His experiments presented a possible explanation of human atherosclerosis and that particular debate has not yet abated. Simultaneously with Anitschkow's studies, A. I. Ignatowski demonstrated the atherogenic potential of animal protein, but compared to work on cholesterol and fat there has only been a desultory interest in protein effects.
Since Anitschkow's results were obtained by dietary manipulation, the view that dietary cholesterol was implicated in atherogenesis was accepted generally. With development of simple, rapid methods of cholesterol analysis, it became possible to screen populations for blood cholesterol content. Large epidemiological studies were launched and their results helped to develop the concept of risk factors for heart disease. Currently, the major risk factors are hypercholesterolemia, hypertension, smoking, obesity, and maleness. However, emerging data suggest that homocysteinemia and inflammation (due to infection with cytomegalovirus or chlamydia pneumoniae) are also important factors.
When cholesterol is ingested, it is emulsified with phospholipid and absorbed. The absorbed lipid circulates in the blood as a water soluble lipid-protein complex called lipoprotein. Initially, absorbed cholesterol is part of a large, triglyceride-rich particle called the chylomicron. In the course of circulation, the triglyceride is removed by activity of cellular lipases and the particles become smaller and their cholesterol content increases. The cholesterol-containing, lipid-protein complex consists of several fractions that are separable by virtue of their hydrated densities. In general terms, the four major fractions are the triglyceride-rich chylomicrons and very low density (VLDL), the cholesterol-rich low density (LDL), and the protein-rich high density (HDL).
Due to development by John Gofman of methods for ultracentrifugal separation of lipoproteins, researchers have been able to isolate and study lipoproteins. The cholesterol-rich low density lipoproteins (LDL) are thought to be major risk factors for coronary disease. It was demonstrated that oxidized LDL is the real villain in coronary disease. It also was shown that LDL can be subfractionated into small, dense and large "fluffy" particles. The small particles appear to infiltrate the artery preferentially. Researchers also know that the process of atherogenesis is not simple and is mediated by an array of small proteins. The high-density lipoproteins are about 50 percent protein. In the simplest terms, LDL facilitates entry of cholesterol into cells and HDL facilitates its removal. LDL receptors on the cell surface facilitate LDL uptake. The proteins of lipoproteins are very important because they provide recognition by cells, and it is now becoming evident that genetic differences in apolipoproteins may dictate susceptibility to disease as well as chances for the efficacy of medication.
The effects of dietary cholesterol became a concern shortly after Anitschkow's observation and warnings regarding excess levels of cholesterol intake, which constitute one of the foundations of dietary therapy. Since cholesterol occurs only in food of animal origin, it was a simple extension to seek an explanation of the role of cholesterol by examining the lipids of food from animal sources. Although no dietary fat is totally saturated or unsaturated, attention also turned to effects of fat saturation.
The amount of cholesterol in the average American diet is in the range of 30050 mg/day. It used to be much higher. The levels of cholesterol in a number of common animal foods are given in Table 2. It is evident that most muscle contains about the same amount of cholesterol, 81 ± 7 mg/100g. Cholesterol content of butter (per 100 g) is high, but we rarely eat more than 50 g of butter per meal. Shrimp is high in cholesterol but very low in fat. Eggs are also high in cholesterol. Continuing research nevertheless indicates that the cholesterol level of a food per se has little effect on serum cholesterol levels. The cholesterolemic effect is a function of dietary fat saturation. It has been shown that the absorption of cholesterol is more a function of the accompanying dietary fat than of cholesterol itself. Saturated dietary fat leads to higher cholesterol levels than does unsaturated fat. This observation is true for most people who are called "non-responders" (to dietary cholesterol). A small number of people are "responders," meaning they absorb more cholesterol, regardless of accompanying fat. In the late 1960s, Keys and Hegsted developed formulas for estimating changes in serum cholesterol based upon changes in dietary fat. There have been a number of more complex formulas developed, but the originals are referred to most often today. Essentially, they found saturated fatty acids to be hypercholesterolemic and unsaturated fatty acids to lower cholesterol. Stearic acid was considered neutral. The polyunsaturated fats lower cholesterol across the board so that HDL cholesterol (the "good" cholesterol) falls as does LDL cholesterol. Oleic acid seems to affect only LDL cholesterol. The reduction in total cholesterol may not be as profound, but the LDL/HDL cholesterol ratio is improved. Recent findings show that the structure of individual triglycerides may also influence their atherogenicity.
In summary, cholesterol is a substance that appears in all cells and also has a number of metabolic functions.
|Cholesterol content (mg/100g) of selected foods|
|Food source||Cholesterol (mg/100g)|
It is synthesized in the body and is part of every cell membrane. Cholesterol is metabolized to adrenocortical or sex hormones, bile acids, and vitamin D. Levels of serum cholesterol are related to risk of coronary disease, but it should be borne in mind that cardiovascular disease is a metabolic disease, not one of cholesterol deposition. Dietary cholesterol is absorbed, but its effects on serum cholesterol are slight. Generally, there is an increase of about 2 mg of serum cholesterol for every 100 mg ingested. Cholesterol should be viewed as a chemical necessary for life and not as a toxic substance. As with so many other aspects of life, moderation is the key.
See also Fats; Health and Disease.
Gibbons, G. F., K. A. Mitropoulos, and Nick B. Myant. Biochemistry of Cholesterol. Amsterdam: Elsevier Biomedical Press, 1982.
Howell, Wanda H., et al. "Plasma Lipid and Lipoprotein Responses to Dietary Fat and Cholesterol: A Meta Analysis." American Journal of Clinical Nutrition 65 (1997): 1747764.
Keys, Ancel, Joseph T. Anderson, and Francisco Grande. "Serum Cholesterol Response to Changes in Diet, IV: Particular Fatty Acids in the Diet." Metabolism 14 (1965): 77687.
Kritchevsky, David. Cholesterol. New York: Wiley, 1958.
Kritchevsky, David. "Food Lipids and Atherosclerosis." In Food Lipids and Health, edited by Richard E. McDonald and David B. Min. New York: M. Dekker, 1996.
Leinoneu, M. "Chlamydia pneumoniae and Other Risk Factors for Atherosclerosis." Journal of Infectious Diseases 181, Suppl. 3 (2000): S414416.
Myant, Nick B. The Biology of Cholesterol and Related Steroids. London: Heinemann Medical Books, 1981.
Myant, Nick B. Cholesterol Metabolism, LDL, and the LDL Receptor. San Diego, Calif.: Academic Press, Inc., 1990.