Cholic acid conjugates

Minder E, Karlaganis G, Schmied U, Vitins P, Paumgartner G (1979) A highly specific 125I-radioimmunoassay for cholic acid conjugates. Clin Chim Acta 92 177-185... 

Bile acids are usually conjugated in amide linkage with the amino acid glycine or taurine, giving bile salts. The cholic acid conjugates with glycine and taurine are called glycocholate and taurocholate, respectively. 

Chemically, the bile acids are hydroxylated derivatives of cholanic acid, a tetracyclic steroid acid of 24 carbon atoms. The acids occur in nature largely as the water-soluble sodium salts of peptide conjugates of glycine and taurine. The free acids are liberated by saponification or specific enzyme hydrolysis. The chemistry of the bile acids has been reviewed in Chapter 1 of this volume (1). In view of their highly polar nature, special attention is called to the recent discovery of the cholic acid conjugates of ornithine (2, 3) and the 3a-sulfate esters of glycolithocholic and taurolithocholic acids (4). 

The principle of the first type of assay is similar to that of RIA a bile acid covalently linked with an enzyme (peroxidase, -galactosidase) is used a tracer instead of a radioisotope. The enzymatic activity of the tracer is recorded spectrophotometri-cally (after antigen-antibody complex separa- on) by measuring specific colour-producing substrates. Mat n developed this method for cholic acid conjugates and Maeda for ursodeoxycholic acid. The sensitivity of these methods is quite similar to corresponding RIA as previously reported (see above). This model of enzyme immunoassay could be extended to other bile acids and this may be used on a large scale in medical laboratories. 

In preliminary experiments he found that neither nuclear nor mitochondrial fractions were necessary for conjugation of cholic acid to taurine. These fractions rather inhibited the conjugation. The recombination of microsomes and soluble fraction (for definition see Section II,C) in the presence of ATP yielded the same conjugation capacity as homogenates. Each of these fractions alone, hoivever, had no conjugation capacity. From those experiments he concluded that the cholic acid conjugating enzyme system must be localized to the microsomes and/or to the soluble fraction and that the same also must be valid for some unknow n cofaetor(s). 

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. 

Swaan, P. W., et al. Enhanced transepithelial transport of peptides by conjugation to cholic acid. Bioconjug. Chem. 1997, 8, 520-525. 

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. 

Before leaving the liver, a large proportion of the bile acids are activated with CoA and then conjugated with the amino acids g/ycine or taurine (2 cf A). In this way, cholic acid gives rise to glycocholic acid and taurocholic acid. The liver bile secreted by the liver becomes denser in the gallbladder as a result of the removal of water (bladder bile 3). 

Glycine conjugation Glycine Acyl-CoA glycinetransferase (mitochondria) Acyl-CoA derivatives of carboxylic acids Salicylic acid, benzoic acid, nicotinic acid, cinnamic acid, cholic acid, deoxycholic acid... 

The C>4 bile acids arise from cholesterol in the liver after saturation of the steroid nucleus and reduction in length of the side chain to a 5-carbon add they may differ in the number of hydroxyl groups on the sterol nucleus. The four acids isolated from human bile include cholic acid (3,7,12-tiihydroxy), as shown in Fig. 1 deoxycholic acid (2,12-dihydroxy) chenodeoxycholic acid (3,7-dihydroxy) and lithocholic acid (3-hydroxy). The bile acids are not excreted into the bile as such, but are conjugated through the C24 carboxylic add with glycine or... 

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