Cholesterol bile acid

Within the small intestine, bile-acid binding interferes with micelle formation. Nauss et al. [268] reported that, in vitro, chitosan binds bile acid micelles in toto, with consequent reduced assimilation of all micelle components, i.e., bile acids, cholesterol, monoglycerides and fatty acids. Moreover, in vitro, chitosan inhibits pancreatic lipase activity [269]. Dissolved chitosan may further depress the activity of lipases by acting as an alternative substrate [270]. 

Steroidogenic type - steroids, bile acids, cholesterol, prostaglandin biosynthesis. 

Cholesterol is doubtless the most publicized lipid, notorious because of the strong correlation between high levels of cholesterol in the blood and the incidence of human cardiovascular diseases. Less well advertised is cholesterol s crucial role as a component of cellular membranes and as a precursor of steroid hormones and bile acids. Cholesterol is an essential molecule in many animals, including humans, but is not required in the mammalian diet—all cells can synthesize it from simple precursors. 

PBS and gently blotted to remove blood and tissue fluids, then suspended over the lip of a small (250 pi) microcentrifuge tube and punctured with a needle to allow the bile to drain into the tube. Store frozen until assay. There is usually enough material to measure lipid composition (bile acids, cholesterol, phospholipids) with standard colorimetric kits (<1 pi needed for each assay). In addition to biliary cholesterol levels, it is important to take note of bile salt concentrations, since these are the detergents which suspend dietary lipids in micelles and deliver them to the intestinal epithelium for absorption by enterocytes. Differences in bile salt concentration alone could lead to differences in cholesterol absorption. 

Bile is a mixture of electrolytes, bile acids, cholesterol, phospholipids and bilirubin. Adults produce between 400 and 800 ml of bile daily. Hepatocytes secrete bile into canaliculi, then into bile ducts, where it is modified by addition of a bicarbonate-rich secretion from ductal epithelial cells. Further modification occurs in the gall bladder, where it is concentrated up to fivefold, through absorption of water and electrolytes. Gallstones, most of which are composed... 

Bile is produced by hepatocytes from several essential components, including water, bile acids, cholesterol, phospholipids and bilirubin. Most of these substances are absorbed in the distal ileum and delivered to the hepatocyte via the portal vein. The liver excretes approximately 500-600 mL of bile each day, most of which is stored in the gallbladder. Bile acids have an important function in emulsifying lipids in the digestive tract, which improves digestion by pancreatic lipases. 

Cholesterol is an extremely important biological molecule that modulates the fluidity of animal cell membranes and is the precursor of steroid hormones (such as progesterone, testosterone, oestradiol and cortisol) and bile acids. Cholesterol is either derived from the diet or synthesised de novo. Regardless of the source, cholesterol is transported through the circulation in lipoprotein particles, as are cholesterol esters, the cellular storage form of cholesterol. The amount of cholesterol synthesised daily in the liver of a normal person is usually double that obtained from dietary sources. Other sites of cholesterol synthesis include the intestine, and the degree of production is highly responsive to cellular levels of cholesterol. Over 1.2 g of cholesterol is lost in the faeces daily in the form of free sterol or as bile acids. 

Bear bile contains bile acids, cholesterol, and phospholipids (phosphatidylcholine, phosphatidylethanolamine, and phos-phatidyhnositol). It has been used for centuries in traditional Chinese medicine to treat liver and eye complaints and convulsions, and, in combination tvith curcuma and capil-laris, gallstones and cholecystitis. More recently it has been touted as a treatment for stroke on the basis of animal experiments. It has few or no adverse effects, but by the same token probably has little or no efficacy, although it does contain ursodeoxycholic acid, which in purified form is effective in managing gallstones. 

Phenanthrene is a polycyclic aromatic hydrocarbon (PAH) that can be derived from coal tar. Phenanthrene is used in the production of dyes, pharmaceuticals, and explosives, and in biochemical research. A derivative, cyclopentenophenanthrene, has been used as a starting material for synthesizing bile acids, cholesterol, and other steroids. 

W. H.J. (1974) Gastric emptying and secretion of bile acids, cholesterol, and pancreatic enzymes during digestion. Duodenal perfusion studies in healthy subjects. Mayo Clin. Proc. 49, 851-860. 

The bile acids are 24-carbon steroid derivatives. The two primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the hepatocytes from cholesterol by hy-droxylation, reduction, and side chain oxidation. They are conjugated by amide linkage to glycine or taurine before they are secreted into the bile (see cholesterol metabolism. Chapter 19). The mechanism of secretion of bile acids across the canalicular membrane is poorly understood. Bile acids are present as anions at the pH of the bile, and above a certain concentration (critical micellar concentration) they form polyanionic molecular aggregates, or micelles (Chapter 11). The critical micellar concentration for each bile acid and the size of the aggregates are affected by the concentration of Na+ and other electrolytes and of cholesterol and lecithin. Thus, bile consists of mixed micelles of conjugated bile acids, cholesterol, and lecithin. While the excretion of osmotically active bile acids is a primary determinant of water and solute transport across the canalicular membrane, in the canaliculi they contribute relatively little to osmotic activity because their anions aggregate to form micelles. 

PXR and CAR Regulation of Bile Acid, Cholesterol and Bilirubin Metabolism... 

Cholestyramine is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low-density lipoprotein [LDL] cholesterol) who do not respond adequately to diet. Similarly, it is indicated for the relief of pruritus associated with partial biliary obstruction. Cholestyramine is not absorbed but binds to bile acids in the intestine, whereupon it is eliminated. To replenish the lost bile acid, cholesterol is then converted to bile acid, and this lowers the level of cholesterol (see Figure 34). Cholestyramine has also been used in the treatment of cholestasis to control the intense pruritis. It reduces the LDL level in 4 to 7 days, and the maximum effect is seen in 14 days. 

Bile salts appear to have a central role in the biliary secretion of water and solutes (103,104). Thus about half of biliary water secretion is bile acid dependent and the other half bile acid independent (104,105). In addition, cholesterol and lecithin secretion is also, at least in part, bile acid dependent. Feeding of bile acids to patients with interrupted enterohepatic circulation has a normalizing effect on the biliary secretion of bile acids, cholesterol and lecithin, so that despite an augmented cholesterol output its solubilization is improved (106,107). When the variation in the biliary bile acid secretion... 

Moreover, due to its facility to form complexes with a different range of molecules, CN seems to have the ability to bind triglycerides, fatty acids and bile acids, cholesterol, and other classes of lipids (Morganti et al. 2008b). 

Ferrous ion-induced Hpid peroxidation of rat liver mitochondria was accelerated by phosphate (Yamamoto et al. 1974). Preincubation of rat liver microsomes with iron (Fe)/ascorbate (50 pM/ 200 pM), known to induce peroxidation, resulted in a significant inhibition of (i) the rate-limiting enzyme in cholesterol biosynthesis, HMG-CoA reductase (46 %, P <0.01, (ii) the crucial enzyme control-Hng the conversion of cholesterol in bile acids, cholesterol 7a-hydroxylase (48%, P <0.001), and (iii) the central enzyme for cholesterol esterification, acyl-CoAxholesterol acyltransferase (ACAT, 80%, P <0.0001) (Brunet etal. 2000). The disturbances of these key enzymes coincided with a high rate of malondialdehyde production (350%, P <0.007) and the loss of polyunsaturated fatty adds (36.19 1.06% vs. 44.24 0.41% in controls, P <0.0008). While a-tocopherol simultaneously neutrahsed lipid peroxidation, preserved microsomal fatty acid status, and restored ACAT activity, it was not effective in preventing Fe/ascorbate-induced inactivation of both HMG-CoA reductase (44%, P <0.01) and cholesterol 7a-hydroxylase (71%, P< 0.0001). 

To summarize, vitamin C is an important mediator of cholesterol metabolism and lipoprotein profile. The rate-limiting enzymes of both cholesterol biosynthesis (HMG-CoA reductase) and cholesterol catabolism to bile acids (cholesterol 7a-hy-droxylase) are affected by vitamin C status. Interestingly, the effect of vitamin C on these enzymes is parabolic with the extremes of vitamin C deficiency and excess... 

Nonsaponifiable lipids are nonpolar compounds that do not form soap. They include steroids, many vitamins, and bile acids. Cholesterol is a steroid present in animal cell membranes and is a precursor of many hormones. 

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