Glycine-conjugated bile salts

Effect of pH. The effect of pH on the deoxycholate series of bile salts in 0.15N NaCl at 20° and 36°C. is summarized in Figure 8. Solutions of free and glycine conjugated bile salts were studied between pH 9.2 and their precipitation pH (NaDC == 6.95, NaGDC = 4.9). Taurine conjugates were studied between pH 10 and 1.6. 

Early studies on the composition of cholestanol-induced gallstones established that they did not contain appreciable amounts of sterol (cholesterol or cholestanol) or pigment but consisted largely of glycine-conjugated bile salts (130,133,139,140). Mosbach and Bevans (139), utilizing cholestanol-14C, demonstrated that approximately half of the bile acids in the stones were... 

These results raise the question of whether these amorphous stones containing calcium bile salts could be related to the pathogenesis of the cholesterol stones. Glycine-conjugated bile salts, particularly of the less soluble compounds such as chenodeoxycholate and lithocholate, have been found in greater proportions in the centers of human gallstones (167), and it would be of interest to know whether this is the case in the cholesterol stones that frequently coexisted in these animals. 

In the case of a free or glycine-conjugated bile salt, the initial solution contains the soluble sodium salt of the bile acid which is fully ionized at high pH (10.5). Titration with HCl is carried out until all the bile acid anion is in the form of an insoluble acid. The chemical reaction in simplified form is... 

Examples of the titration curves for a pure bile salt (NaC) and pure conjugated bile salt solutions (NaGC and NaTC) are shown in Fig. 24. The curves for sodium cholate and sodium glycocholate are similar to the ideal curve (Fig. 21), but since sodium taurocholate is the salt of a strong acid and remains completely ionized, the solution remains clear throughout the titration and therefore neither the supersaturation nor the precipitation characteristic of the free and glycine-conjugated bile salts takes place. 

Additional reactions of glycine include its ability to become conjugated with bile acids to form conjugated bile salts (see Chapter 19), formation of heme (Chapter 7), formation of purine nucleotides (Chapter 10), formation of creatine (see later), and the formation of hippuric acid from benzoic acid. In the last case, an amide linkage is formed between the carboxyl group of benzoic acid and the amino group of glycine. 

Glycocholic acid, and glycocheno-Deoxycholic acid Glycine, bile salts Liver Conjugated bile salts are excreted into the bile and assist in the absorption of lipids and fat-soluble vitamins through the formation of micelles... 

In humans as in animals the primary bile acids are converted in various ways, and more than 25 different secondary bile acids have been identified in human feces. Deoxycholate and lithocholate stand out because they are found in large quantities. These secondary bile acids are derived from cholate and chenodeoxycholate through 7-dehydroxylation by enzymes of colonic bacteria. In man, primary and secondary bile salts are all conjugated to two amino acids, taurine and glycine, and thus the amounts of free bile salts are very small. Conjugated bile salts... 

If there is reason to suspect the presence of several salt forms, one should convert the bile acids into only one form before attempting a chromatography in neutral organic solvents. This can be done with the cation exchanger Amberlyst A-15 [free and glycine-conjugated bile acids can be extracted with ethyl acetate from an acidified water solution but this cannot be done with... 

Mammalian bile contains sodium salts of conjugated bile acids, e.g. glycocholic acid and taurocholic acid, in which cholic acid is combined (amide linkage) with glycine and taurine respectively. 

Bile acids, which exist mainly as bile salts, are polar carboxylic acid derivatives of cholesterol that are important in the digestion of food, especially the solubilization of ingested fats. The Na and salts of glycocholic acid and tauro-cholic acid are the principal bile salts (Ligure 25.41). Glycocholate and tauro-cholate are conjugates of cholic acid with glycine and taurine, respectively. 

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. 

Cholic acid and chenodeoxycholic acid, known as the primary bile acids, are quantitatively the most important metabolites of cholesterol. After being biosynthesized, they are mostly activated with coenzyme A and then conjugated with glycine or the non-pro-teinogenic amino acid taurine (see p. 62). The acid amides formed in this way are known as conjugated bile acids or bile salts. They are even more amphipathic than the primary products. 

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