Bile Acids

The Gallstone Elimination Report

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The bile acids* are C24 steroidal acids that occur in salt form in bile, secreted into the gut to emulsify fats and encourage digestion. They act as detergents by virtue of their relatively non-polar steroid nucleus and the polar side-chain, which contains a carboxylic acid group, that is typically bound via an amide linkage to glycine or taurine. Thus, for example, cholic acid (Figure 5.108) is found as sodium glycocholate and sodium tauro-cholate. Metabolism to bile acids is also the principal way in which mammals degrade cholesterol absorbed from the diet. These structures are formed in the liver from cholesterol by a sequence which oxidizes off three carbons from the side-chain (Figure 5.109). This is achieved by initial oxidation of one of the side-chain methyls to an acid, followed by a ^-oxidation sequence as seen with fatty acids (see Figure 2.11), removing the three-carbon unit as propionyl-CoA. Other essential features of the molecule are introduced earlier. The A/B ring system is ds-fused, and this is achieved by reduction of a A4 rather than a A5 double bond (see page 241). Migration of the double bond is accomplished via the 3-ketone, and when this is reduced back to a hydroxyl the configuration at C-3 is changed to 3a. Both cholic acid and chenodeoxy-cholic acid (Figure 5.110) are formed in the liver, though the 7a-hydroxyl functions of these compounds can be removed by intestinal microflora, so that mammalian bile also contains deoxycholic acid and lithocholic acid (Figure 5.110). The bile salts are then usually reabsorbed and stored in the gall bladder, although they are also excreted as the body's main means of eliminating excess cholesterol. Inability to remove cholesterol by bile acid synthesis and excretion may contribute to atherosclerosis and gallstone disease; gallstones often contain more than 70% of cholesterol.

Cholesterol Bile

7a-hydroxylation; oxidation of reduction of 4,5-double bond gives

3-hydroxyl leads to A4-3-ketone, cis-fused rings; stereospecific reduction of

O then 12a-hydroxylation carbonyl generates 3a-hydroxyl

7a-hydroxylation; oxidation of reduction of 4,5-double bond gives

3-hydroxyl leads to A4-3-ketone, cis-fused rings; stereospecific reduction of

O then 12a-hydroxylation carbonyl generates 3a-hydroxyl

Glycocholate Polar Nonpolar

propionyl-CoA

Figure 5.109

propionyl-CoA

Figure 5.109

Figure 5.110

R = OH, cholic acid R = OH, deoxycholic acid

R = H, chenodeoxycholic acid R = H, lithocholic acid

Figure 5.110

Bile Acids

Bile acids are obtained by purification from fresh ox bile taken from carcasses as a byproduct of the meat trade. Chenodeoxycholic acid (Figure 5.110) and ursodeoxycholic acid (Figure 5.111) are used to dissolve cholesterol gallstones as an alternative to surgery. By suppressing synthesis of both cholesterol and cholic acid, they contribute to removal of biliary cholesterol and consequently a gradual dissolution of gallstones which may have formed due to supersaturation. Partial or complete dissolution requires treatment over a period of many months, and is not effective for radio-opaque gallstones, which contain appreciable levels of calcium salts. Dehydrocholic acid (Figure 5.111) may be used, after surgery, to improve biliary drainage. Anion-exchange resins such as colestyramine (cholestyramine) and colestipol are used as cholesterol-lowering drugs to bind bile acids and prevent their reabsorption. This promotes hepatic conversion of cholesterol into bile acids, thus increasing breakdown of low density lipoprotein cholesterol, and is of value in treating high risk coronary patients.

ursodeoxycholic acid

CO2H

ursodeoxycholic acid

dehydrocholic acid

CO2H

dehydrocholic acid

Figure 5.111

Bile acids are still important as starting materials for the semi-synthesis of other medicinal steroids, being a cheap and readily accessible raw material.

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Get Rid of Gallstones Naturally

Get Rid of Gallstones Naturally

One of the main home remedies that you need to follow to prevent gallstones is a healthy lifestyle. You need to maintain a healthy body weight to prevent gallstones. The following are the best home remedies that will help you to treat and prevent gallstones.

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