Cholesterol disease

Cholesterol is biosynthesized in the liver trans ported throughout the body to be used in a va riety of ways and returned to the liver where it serves as the biosynthetic precursor to other steroids But cholesterol is a lipid and isn t soluble in water How can it move through the blood if it doesn t dis solve in if The answer is that it doesn t dissolve but IS instead carried through the blood and tissues as part of a lipoprotein (lipid + protein = lipoprotein) The proteins that carry cholesterol from the liver are called low density lipoproteins or LDLs those that return it to the liver are the high-density lipoproteins or HDLs If too much cholesterol is being transported by LDL or too little by HDL the extra cholesterol builds up on the walls of the arteries caus mg atherosclerosis A thorough physical examination nowadays measures not only total cholesterol con centration but also the distribution between LDL and HDL cholesterol An elevated level of LDL cholesterol IS a risk factor for heart disease LDL cholesterol is bad cholesterol HDLs on the other hand remove excess cholesterol and are protective HDL cholesterol IS good cholesterol... 

Low density lipoprotein (LDL) (Section 26 11) A protein which cames cholesterol from the liver through the blood to the tissues Elevated LDL levels are a nsk factor for heart disease LDL is often called bad cholesterol... 

The path from squalene (114) to the corresponding oxide and thence to lanosterol [79-63-0] (126), C qH qO, cholesterol [57-88-5] (127), and cycloartenol [469-38-5] (128) (Fig. 6) has been demonstrated in nonphotosynthetic organisms. It has not yet been demonstrated that there is an obligatory path paralleling the one known for generation of plant sterols despite the obvious stmctural relationships of, for example, cycloartenol (128), C qH qO, to cyclobuxine-D (129), C25H42N2O. The latter, obtained from the leaves of Buxus sempervirens E., has apparentiy found use medicinally for many disorders, from skin and venereal diseases to treatment of malaria and tuberculosis. In addition to cyclobuxine-D [2241-90-9] (129) from the Buxaceae, steroidal alkaloids are also found in the Solanaceae, Apocynaceae, and LiUaceae. 

Unfortunately, excess consumption of fatty foods has been correlated with serious human disease conditions. Effects on cardiovascular disease (95), cancer (96), and function of the immune system (97) have been shown. Numerous studies have been conducted to determine the effects of saturated, monounsaturated, and polyunsaturated fatty acids on semm cholesterol and more recently high density Hpoprotein (HDL) and low density Hpoprotein... 

Diseases. Liquid crystals have been impHcated in a number of disease conditions in the human body. A complex cholesterol—phosphoHpid—Hpoprotein Hquid crystal phase has been identified in the initiation and maintenance of atheromatous deposits on the aortic intima in dissected human and rabbit arteries (40). The paracrystalHne nature of this precursor to plaque buildup with the resultant loss of arterial elasticity... 

Defects in the LDL receptor have been particularly well explored as a basis of the disease familial hypercholesterolemia (93,111). A number of defects that collectively impair LDL receptor trafficking, binding, or deUvery underHe this disease where LDL and semm cholesterol rise to levels that mediate early cardiovascular mortaUty. Studies of the population distribution of this defect can determine the source of the original mutation. Thus, in Quebec, about 60% of the individuals suffering from familial hypercholesterolemia have a particular 10-kdobase deletion mutation in the LDL gene (112). This may have arisen from an original founder of the French Canadian settiement in the seventeenth century. 

G. Paumgartner, A. Stiehl, and W. Gerok, eds.. Bile Acids and Cholesterol in Health and Disease, MTP Press Ltd, Boston, Mass., 1983. 

The possibility that vitamins might have physiological functions beyond the prevention of deficiency diseases was first recognized in 1955 with the finding (8) that niacin can affect semm cholesterol levels in humans. An explosion of research (9—11) in the intervening years has been aimed at estabUshing optimal vitamin levels and anticipating the health consequences. 

Reduction in semm Hpids can contribute significantly to prevention of atherosclerosis. In 1985 a consensus report indicating that for every 1% reduction in semm cholesterol there is a 2% reduction in adverse effects of coronary heart disease was issued (145). Recommended semm cholesterol concentration was 200 mg/dL for individuals under 30 years of age, and individuals having concentration 240 mg/dL and LDL-cholesterol over 160 mg/dL should undertake dietary modification and possibly pharmacotherapy (146). Whereas the initial step in reducing semm cholesterol is through reduction of dietary cholesterol intake, a number of dmgs are available that can affect semm Hpid profile (see Fat substitutes). The pathway to cholesterol synthesis is shown in Figure 2. 

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

Thus, it is apparent that soya, some soya products and linseed oil influence blood lipid levels, particularly cholesterol and LDL cholesterol. While the extent of the reduction appears to largely depend on an individual s initial serum cholesterol level, the maximum reductions observed are of the order of 10-15%. For hyperlipidemic individuals this may not be a marked reduction, but such an effect on the general population may well have a beneficial effect on the overall incidence of cardiovascular disease and atherosclerosis. The possibility that non-phytoestrogenic dietary components may contribute to the hypocholes-terolemic properties cannot, however, be discounted. Indeed, certain types of dietary fibre have been shown to have a hypolipidemic effect via their ability to increase faecal excretion rates. 

Atherosclerosis is a degenerative disease which is characterized by cholesterol-containing thickening of arterial walls. Saturated fatty acids, high levels of cholesterol, elevated blood pressure, and elevated serum lipoprotein are well-knowm risk... 

Compare and contrast two individuals, one of whose diet consists largely of meats containing high levels of cholesterol, and the other of whose diet is rich in plant sterols. Are their risks of cardiovascular disease likely to be similar or different Explain your reasoning. 

High-density lipoproteins (HDL) have much longer life spans in the body (5 to 6 days) than other lipoproteins. Newly formed HDL contains virtually no cholesterol ester. However, over time, cholesterol esters are accumulated through the action of lecithin cholesterol acyltransferase (LCAT), a 59-kD glycoprotein associated with HDLs. Another associated protein, cholesterol ester transfer protein, transfers some of these esters to VLDL and LDL. Alternatively, HDLs function to return cholesterol and cholesterol esters to the liver. This latter process apparently explains the correlation between high HDL levels and reduced risk of cardiovascular disease. (High LDL levels, on the other hand, are correlated with an increased risk of coronary artery and cardiovascular disease.)... 

We hear a lot these days about the relationships between saturated fats, cholesterol, and heart disease. What are the facts It s well established that a diet rich in saturated animal fats often leads to an increase in blood serum cholesterol, particularly in sedentary, overweight people. Conversely, a diet-lower in saturated fats and higher in polyunsaturated fats leads to a lower serum cholesterol level. Studies have shown that a serum cholesterol level greater than 240 mg/dL (a desirable value is <200 mg/dL) is correlated with an increased incidence of coronary artery disease, in which cholesterol deposits build up on the inner walls of coronary arteries, blocking the flow of blood to the heart muscles. 

Focus On... Saturated Fats, Cholesterol, and Heart Disease 1090... 

LDL, or "bad," cholesterol builds up as a plaque-like deposit on the interior walls of arteries. This process used to be called hardening of the arteries today it is referred to as atherosclerosis. It can lead to cardiovascular diseases, including strokes and heart attacks. In contrast, HDL or "good" cholesterol retards or even reduces arterial deposits. 

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