Cholic acid from bile salts

FIGURE 25.41 Cholic acid, a bile salt, is synthesized from cholesterol via 7o -hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents. 

Bacteria in the intestine can remove glycine and taurine from bile salts, regenerating bile acids. They can also convert some of the primary bile acids into "secondary" bile acids by removing a hydroxyl group, producing deoxycholic acid from cholic acid and lithocholic acid from chenodeoxycholic acid (Figure 18.11). 

Two primary bile acids are synthesized in the liver from cholesterol. These are cholic acid and chenodeoxycholic acid. They are conjugated with the amino acids, glycine and taurine, to form bile salts (for example taurine may be conjugated with cholic acid to give taurocholic acid). The bile salts are excreted in the bile, and in the gut they are acted upon by bacteria which convert them to the secondary bile acids, deoxycholic acid and lithocholic acid. Some of the secondary bile acids are absorbed and carried by the enterohepatic circulation to the liver where they are re-excreted. 

Certain compounds are known to achieve higher absorption rates from the GI tract if they are taken with food, and this observation has been linked to their solubilization by bile salts [74], Bile salts, especially those of cholic and deoxycholic acids, have been used to solubilize steroid hormones [75], antibiotics [76], and nonsteroidal antiinflammatory drugs [77]. For example, amphotericin B (an antifungal agent) has been solubilized for parenteral use in micelles composed of sodium desoxycholate [78], As illustrated in Fig. 11, the degree of solubilization of carbamazepine by sodium desoxycholate is minimal below the critical micelle concentration but increases rapidly above this value [79]. At sufficiently high concentrations, when the micelles become saturated in carb-amezepine, the apparent solubility reaches a limiting value approximately seven times the true aqueous solubility in the absence of desoxycholate. 

The aggregation behavior of C21-DA salt in dilute electrolyte medium appears to resemble that of certain polyhydroxy bile salts (25,16). That C21-DA, with a structure quite different from bile acids, should possess solution properties similar to, e.g., cholic acid is not entirely surprising in light of recent conductivity and surface tension measurements on purified (i.e., essentially monocarboxylate free) disodium salt aqueous solutions, and of film balance studies on acidic substrates (IX) The data in Figure 3 suggest that C21-DA salt micelles Incorporate detergents - up to an approximate weight fraction of 0.5 -much like cholate Incorporates lecithin or soluble... 

Part of the cholesterol newly synthesized in the liver is excreted into bile in a free non-esterified state (in constant, amount). Cholesteiol in bile is normally complexed with bile salts to form soluble cholic acids, Free cholesterol is not readily soluble and with bile stasis or decreased bile salt concentration may precipitate as gallstones. Most common gallstones are built of alternating layers of cholesterol and calcium bilirubin and consist mainly (80-90%) of cholesterol. Normally. 80% of hepatic cholesterol arising from blood or lymph is metabolized to cholic acids and is eventually excreted into the bile in the form of bile salts. 

Bile Salts Enable the Digestion of Lipids Cholesterol is the precursor of both steroids and bile salts and is an integral component of cell membranes. It is eliminated from the body via conversion to bile salts and direct secretion into the bile. In fact, the word cholesterol (from the Greek chole (bile) and stereos (solid)) was used originally to describe the material of which gallstones are made. In the process of degradation, it is converted to the primary bile acids cholic acid and chenodeoxycholic acid in approximately equal amounts. The salts of these acids are excreted in bile. They perform two important functions in the digestive tract ... 

OX BILE, Fel taurisOn bile is obtained from cattle in slaughterhouses, and contains sodium salts of some 20 conjugated bile acids. Among these, cholic acid and desoxy-cholic acid occur in the ratio 10 1. 

Rosinate and Cholate. These carboxylates were included because of their different (from fatty acid) structure rosin acids compose about half of the tall oil acids and cholic acid is a representative bile acid that is important in the animal metabolism of fats. Salts of these acids had interfacial tensions that were significantly higher than oleate no minima were found (Figure 7)-... 

Chimaerol sulfate is the chief bile salt of Chimaera monstrosa [10], and also occurs as a minor companion of scymnol sulfate in the bile of elasmobranchii [11.12], 5/3-Chimaerol was characterized as 5 8-cholestane-3a,7a,12a,24,26-pentol by comparison with synthetic samples prepared from cholic acid [3] and from anhydroscymnol [1],... 

The major bile salt of the carp, Cyprinm carpio, is 5a-cyprinol sulfate [21]. When [4- C]cholesterol was injected intraperitoneally into the carp, radioactive 5a-cyprinol was isolated from gallbladder bile [148]. It has been shown that the initial step in the major pathway for the formation of 5a-cyprinol (VI) from cholesterol (XV) is the 7a-hydroxylation of cholesterol to form cholest-5-ene-3j8,7a-diol (XVI) [149] (Fig. 4). It has also been shown that the double bond is isomerized to the A position before being reduced [150]. These in vivo studies suggest that until the intermediary formation of a A compound, presumably 7 ,12a-dihydroxycholest-4-en-3-one (XVII), the sequence of reactions in the biosynthesis of 5 -cyprinol (VI) in the carp is the same as that in the conversion of cholesterol (XV) to cholic acid (XIV) in mammals. 7a,12a-Dihydroxycholest-4-en-3-one (XVII) was found to be converted into 5a-cholestane-3a,7a,12a-triol (XVIII) by the microsomal fraction of carp hver fortified with NADPH [151]. The conversion of the triol (XVIII) to 5a-cyprinol (VI) via 27-deoxy-5a-cyprinol (XIX) was also established. The 26-hydroxylation of the triol (XVIII) was catalyzed by the microsomal fraction fortified with NADPH, and the 27-hydroxylation of 27-deoxy-5a-cyprinol (XIX) was catalyzed by the mitochondrial fraction fortified with NADPH [151]. 

Hoshita et al. have shown that liver microsomes from the green iguana, in which the major biliary bile salt is tauroallocholate, convert 7a,12a-dihydroxycholest-4-en-3-one (XVII) into 5a-cholestane-3a,7a,12a-triol (XVIII) rather than into 5)8-choles-tane-3 ,7a,12a-triol (VIII) which is involved in cholic acid biosynthesis [164]. On the basis of this result and that obtained from studies with carp liver [151], it can be assumed that 5a-bile acids and alcohols are formed from cholesterol by a modification of the biosynthetic pathway to the corresponding 5y8 isomers in which the only difference is the stereospedfic saturation of the A double bond of the intermediate XVII. 

Huijghebaert et al. [23] isolated a bile salt sulfatase-producing strain designated, Clostridium S, from rat feces. This bacterium hydrolyzed the 3-sulfates of lithocholic acid, chenodeoxycholic acid, deoxycholic acid and cholic acid but not the 7-or 12-monosulfates. Sulfatase activity required the 3-sulfate group to be in the equatorial position. A free C-24 or C-26 carboxyl group was also required for sulfatase activity in whole cells of this bacterium. The 3-sulfate of cholesterol, Cj,-and Cji-steroids were not hydrolyzed by Clostridium S, [24]. Nevertheless, C,9- and C2]-steroid sulfates are hydrolyzed in the gut by microbial activity suggesting that the intestinal microflora may contain bacteria with steroid sulfatases possessing different substrate specificities. However, it should be noted that enzyme substrate specificity studies carried out in whole cells may reflect both cell wall permeability and enzyme specificity. 

Tiurooholic acid—C, H,jNO,w—515—(ckofeic acid of Strecker)— exists os its sodium salt in the bile of man and of the carnivora, and in much less abundance in that of the herbivora in the bile of the dog it seems to be unaccompanied by any other biliary acid. It may be obtained from dog s bile by a modification of the method described under glyoo-cholic acid the watery solution is not treated with as in the... 

See also Figure 19.23, Bile Salts and Emulsion of Fats, Bile Acids (from Chapter 19), Fats, Glycine, Taurine, Glycocholate, Taurocholate, Cholic Acid... 

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