Bile, acid cholesterol absorption

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 acid sequestrates are anion-exchange resins, which sequester bile acid in the intestine. Cholestyramine and colestipol are the most commonly used in this category, which by this mechanism prevents bile acid re-absorption and causes decreased absorption of exogenous cholesterol and increased metabolism of endogenous cholesterol into bile acid in the liver by preventing enterohepatic recirculation. This leads to an increased expression of LDL receptors in liver and causes increased removal of LDL from blood and reduces the LDL cholesterol in the plasma. 

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... 

D. Cholestyramine binds bile acids strongly so that they cannot be reabsorbed in the intestinal tract, thus increasing the flow of cholesterol to bile acid synthesis and decreasing cholesterol levels in the plasma. However, by binding bile acids, cholestyramine also decreases the absorption of fat-soluble vitamins and fatty acids, which must be taken up in micelles formed with bile acids. Although absorption of vitamin A and linolenic acid may be compromised, the patient needs to be concerned about vitamin K, which is required for blood clot formation. 

Matseshe, Effect of B-sitosterol alone or in combination with chenic acid on cholesterol saturation of bile and cholesterol absorption in gallstone patients. Gastroenterology, 76 1341-1346 (1979). 

Anion exchange resins are basic polymers with a high affinity for anions. Because different anions compete for binding to them, they can be used to sequester anions. Clinically used anion exchange resins such as cholestyramine are used to sequester bile acids in the intestine, thereby preventing their reabsorption. As a consequence, the absorption of exogenous cholesterol is decreased. The accompanying increase in low density lipoprotein (LDL)-receptors leads to the removal of LDL from the blood and, thereby, to a reduction of LDL cholesterol. This effect underlies the use of cholestyramine in the treatment of hyperlipidaemia. 

Although products of fat digestion, including cholesterol, are absorbed in the first 100 cm of small intestine, the primary and secondary bile acids are absorbed almost exclusively in the ileum, and 98—99% are returned to the liver via the portal circulation. This is known as the enterohepatic circulation (Figure 26—6). However, lithocholic acid, because of its insolubility, is not reabsorbed to any significant extent. Only a small fraction of the bile salts escapes absorption and is therefore eliminated in the feces. Nonetheless, this represents a major pathway for the elimination of cholesterol. Each day the small pool of bile acids (about 3-5 g) is cycled through the intestine six to ten times and an amount of bile acid equivalent to that lost in the feces is synthesized from cholesterol, so that a pool of bile acids of constant size is maintained. This is accomplished by a system of feedback controls. 

SEETHARAMIAH G s, CHANDRASEKHARA N (1990) Effect of gamma oryzanol on cholesterol absorption and biliary and fecal bile acids in rats. Ind J Med Res, 92 471-5. 

Bile acids secreted into the small intestine facilitate absorption of fat-soluble vitamins and cholesterol. The majority of bile acids are reabsorbed from the intes-... 

In addition to more rapid absorption of lipids in animals fed casein, another mechanism that may be operative is decreased clearance of circulating lipids. Rabbits fed a casein-based semipurified diet excreted significantly less cholesterol but more bile acids in their feces than animals fed a commercial diet (18). The total sterol excretion in feces of the animals fed the casein diet was half that of the rabbits fed the stock diet. Huff and Carroll (19) found that rabbits fed soy protein had a much faster turnover rate of cholesterol and a significantly reduced rapidly exchangeable cholesterol pool compared with rabbits fed casein. Similar studies performed in our laboratory revealed that the mean transit time for cholesterol was 18.4 days in rabbits fed soy protein, 36.8 days in rabbits fed casein, 33.7 days in rabbits fed soy plus lysine, and 36.3 days in rabbits fed casein plus arginine. These data suggest that addition of lysine to soy protein... 

Bile salts consist of taurine linked to bile acids. The salts are essential for digestion and absorption of fat and also of fat-soluble vitamins and cholesterol. 

Bile helps in the digestion and absorption of fats. Its constituent bile acids (BAs) have detergent properties, and some can be carcinogenic. BAs can act as signalling molecules, entering the nuclei and reacting with the nuclear receptors and this could enhance or reduce BA synthesis. In this way, they control their own levels as well as those of their precursor, cholesterol. This controls cholesterol homeostasis and BA and lipid synthesis. 

SREBP2. High levels of cholesterol would reduce levels of ASBT and reduce bile-acid absorption in the ileum. 

The most common assay uses 3a-hydroxysteroid dehydrogenase to form the 3-keto bile acid that is trapped by, for example, hydrazine hydrate, causing the reaction to go to completion. The co-factor NAD is reduced stoichiometrically and can be measured by ultraviolet absorption or more commonly by fluorescence at an activation of 345 nm and emission of 450 nm. Use of this enzyme measures all bile acids with a 3a-hydroxyl but not cholesterol, which has a 3p-hydroxyl, and does not measure bile acids with a sulphate or glucuronide group conjugated to the 3a-hydroxyl. 

As discussed above, obesity is associated with dyslipidemia, a condition where high levels of low-density lipoprotein cholesterol (LDL-C) is common. Elevated LDL-C is strongly associated with an elevated risk of coronary artery disease and for this reason a number of lipid-lowering therapies that target LDL-C have been developed. These include bile-acid sequestrants (BAS), statins (HMG-CoA reductase inhibitors), cholesterol absorption inhibitors, and fibrates. ... 

Questran, which is colestyramine, binds to bile acids resulting in prevention of their re-absorption and hence promoting hepatic conversion of cholesterol into bile acids. 

Hypolipidemic activity. Seed hull, administered to mice at a dose of 2.5% of diet for 18 weeks, was inactive " . The husk, administered orally to male Hartley guinea pigs at doses of 7.5 or 10 g/100 g of Plantago ovata for 4 weeks, exerted a hypolipidemic effect by affecting bile acid absorption and altering hepatic cholesterol metabolism Insulin release inhibition. Seed administered orally to 18 patients with noninsulin-dependent diabetes at a dose of 13.6 g/day lowered insulin levels by 17% . 

In addition to treatment with the statins, hypercholesterolemia is sometimes treated with the use of nonabsorbable anion-exchange resins like cholestyramine (5.13) and colestipol, which sequester bile acid in the intestine, excrete them, and thus increase their synthesis in the liver by a feedback mechanism. Increased bile acid synthesis increases cholesterol metabolism and also decreases LDL concentrations. Unfortunately, these resins interfere with the absorption of other fats and fat-soluble vitamins (A, D, E, and K). They... 

Colestipol Binds bile acids in gut prevents reabsorption increases cholesterol catabolism up-regulates LDL receptors Decreases LDL Elevated LDL, digitalis toxicity, pruritus Oral taken with meals not absorbed Toxicity Constipation, bloating interferes with absorption of some drugs and vitamins... 

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