Cholesterol product

PARKER R A, PEARCE B 0, CLARK R w, GORDON D A, WRIGHT J J (1993) Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy 3-methyl-glutaryl-coenzyme A reductase. J Biol Chem, 268 11230-38. 

In the bile cholesterol is kept soluble by fats, phospholipids like lecithin and by bile acids. The important bile acids in human bile are cholic acid, chen-odeoxycholic acid or chenodiol and ursodeoxycholic acid or ursodiol. Bile acids increase bile production. Dehydrocholic acid, a semisynthetic cholate is especially active in this respect. It stimulates the production of bile of low specific gravity and is therefore called a hydrocholeretic drug. Chenodiol and ursodiol but not cholic acid decrease the cholesterol content of bile by reducing cholesterol production and cholesterol secretion. Ursodiol also decreases cholesterol reabsorption. By these actions chenodiol and ursodiol are able to decrease the formation of cholesterolic gallstones and they can promote their dissolution. 

Pravastatin sodium besides increasing LDL cholesterol catabolism, also inhibits LDL-cholesterol production by inhibiting hepatic synthesis of VLDL-cholesterol, the LDL-cholesterol precursor. These effects result in a reduction of total cholesterol, LDL-cholesterol, VLDL-cholesterol, apolipoprotein B and trigly-cerides, whilst increasing (HDL-cholesterol) and apolipoprotein A. It has little effect on cholesterol synthesis in other tissues. 

Cholesterol is present in milk at a level of 0.25-0.46%. The interest in removing cholesterol from milk fat has been driven primarily by consumer concern about the possible link between cholesterol and heart disease. Although there is still some debate about the causal relationship between dietary cholesterol and heart disease, a marketing position has been created for low-cholesterol products and this has spurred interest in examining alternative ways of cholesterol removal in the 1980s and 1990s (Schlimme, 1990). A number of physical, chemical and biological processes have been used to reduce the level of cholesterol in milk fat (Boudreau and Arul, 1993). Cholesterol-reduced butter has been introduced on the market in Europe (Anon, 1992). 

Figure 18.5. Formation of some minor cholesterol products. Compounds are as follows (1) CHOL (2) 3-keto-5-en (3) 3-keto-4-en (4) 6a-OOH (5) 6(3-OOH. For abbreviations, see Table 18.1.

In this study, both groups of exercised animals had lower plasma total cholesterol and chylomicron cholesterol than appropriate sedentary control animals (Table VI). Unexpectedly, plasma HDL cholesterol was also lower in both groups of exercised animals (Table VI). Together with the results obtained on hepatic HDL cholesterol production, these data demonstrate that plasma HDL cholesterol concentration reflects hepatic HDL cholesterol production in obese, but not in lean rats. 

Table VI. Plasma Total, Chylomicron, and HDL Cholesterol and Hepatic HDL Cholesterol Production In Lean and Obese Zucker Rats In Response to Exercise...

In suiamary, It appears that hepatic HDL cholesterol production is altered with exercise. Factors such as adiposity and diet, and others that are as yet unidentified, may mask the detection of changes in HDL cholesterol production with exercise. 

Therefore, the nature of the oxygenated cholesterol products in atherosclerotic human aorta does not exclude the fact, that they have been formed during lipoxygenase catalysis. Really, our results demonstrated that the activity of C-15 animal lipoxygenase may be greatly stimulated by addition of the atherogenic LDL to the incubation media [21,22] (Figure 6). 

Various experiments on animals and humans had shown that cholesterol could either be absorbed from the diet, or if the diet was lacking sufficient cholesterol to meet the body s needs, then it could be synthesized. Cholesterol production within the body is controlled by a feedback mechanism in which cholesterol inhibited the enzyme HMG CoA reductase, an enzyme discovered in 1959 by Feodor Lynen et al. (Figure 1.36) at the Max Planck Institute (Munich).24 ... 

AFM was used to investigate whether a series of related molecules could be analyzed when present as SAM. The system chosen was the cholesterol molecule. The molecule cholesterol is a very important biological lipid. A cholesterol molecule with one hydroxyl group is known to oxidize into a variety of structures. These oxidized cholesterol products play an important role in many biological diseases, such as blood clots. The AFM data of the collapsed film of cholesterol (when spread on the surface of water) shows that two-dimensional crystallization takes place with very characteristic butterfly shapes. This shows, for the first time in the literature, that not all lipid monolayers collapse to give a transition from monolayer to trilayer. This shows that the collapsed state may be a two-dimensional crystal phase. 

Unregulated cholesterol production can lead to serious human disease. When the sum of cholesterol synthesized and cholesterol obtained in the diet exceeds the amount required for the synthesis of membranes, bile salts, and steroids, pathological accumulations of cholesterol in blood vessels (atherosclerotic plaques) can develop, resulting in obstruction of blood vessels (atherosclerosis). Heart failure due to occluded coronary arteries is a leading cause of death in industrialized societies. Atherosclerosis is linked to high levels of cholesterol in the blood, and particularly to high levels of LDL-bound cholesterol there is negative correlation between HDL levels and arterial disease. 

To date, no plausible explanation has been forwarded as to why such increase in cholesterol production should occur. Here, we propose an explanation, which suggests that the cholesterol variations can be attributed to the fluctuations in the amount of the active species of the enzyme. 

Tomatoes also contain phenolic acids and plant sterols. These are also considered to be protectors against cancer. They also contain monoterpenes. These are antioxidants that protect against cancer and prevent cholesterol production. 

Bile acids have two major functions in man (a) they form a catabolic pathway of cholesterol metabolism, and (b) they play an essential role in intestinal absorption of fat, cholesterol, and fat-soluble vitamins. These functions may be so vital that a genetic mutant with absence of bile acids, if at all developed, is obviously incapable of life, and therefore this type of inborn error of metabolism is not yet known clinically. A slightly decreased bile acid production, i.e., reduced cholesterol catabolism, as a primary phenomenon can lead to hypercholesterolemia without fat malabsorption, as has been suggested to be the case in familial hypercholesterolemia. A relative defect in bile salt production may lead to gallstone formation. A more severe defect in bile acid synthesis and biliary excretion found secondarily in liver disease causes fat malabsorption. This may be associated with hypercholesterolemia according to whether the bile salt deficiency is due to decreased function of parenchymal cells, as in liver cirrhosis, or whether the biliary excretory function is predominantly disturbed, as in biliary cirrhosis or extrahepatic biliary occlusion. Finally, an augmented cholesterol production in obesity is partially balanced by increased cholesterol catabolism via bile acids, while interruption of the enterohepatic circulation by ileal dysfunction or cholestyramine leads to intestinal bile salt deficiency despite an up to twentyfold increase in bile salt synthesis, to fat malabsorption, and to a fall in serum cholesterol. 

It seems evident that (1) if bile acid elimination is inhibited or impaired as a primary phenomenon, e.g., in biliary obstruction and hypercholesterolemia, a decreased catabolism of cholesterol leads to hypercholesterolemia and reduced cholesterol synthesis (2) if bile acid elimination is primarily augmented, e.g., after an external bile fistula, ileal bypass, ileal resection, cholestyramine treatment, or perhaps a diet rich in fibrous material, conversion of cholesterol to bile acids is enhanced, leading almost always, despite stimulated cholesterol synthesis, to a fall in serum cholesterol (3) if endogenous cholesterol production is primarily increased, e.g., by obesity and excess of calories, bile acid synthesis and elimination are augmented, preventing together with increased neutral sterol elimination in some but not all cases the increase of serum cholesterol. This suggests that removal, not production, of cholesterol is the primary factor which determines serum cholesterol level. 

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