Bile acids epimerization

Figure 2 also shows that spectra of trifluoroacetates of epimeric bile acids are very similar. Some examples given below indicate that trimethylsilyl ethers give more discriminating spectra in analyses of epimers. There are numerous examples of differences between spectra of trimethylsilyl ethers of... 

Oxidoreduction of hydroxyl groups by intestinal organisms is associated with the formation of epimerized bile acids via ketonic intermediates (Figure 1). 3a-, 63-, 7a-, 73- and 12a-hydroxysteroid... 

The intestinal microflora of man and animals can biotransform bile acids into a number of different metabolites. Normal human feces may contain more than 20 different bile acids which have been formed from the primary bile acids, cholic acid and chenodeoxycholic acid [1-5], Known microbial biotransformations of these bile acids include the hydrolysis of bile acid conjugates yielding free bile acids, oxidation of hydroxyl groups at C-3, C-6, C-7 and C-12 and reduction of oxo groups to give epimeric hydroxy bile acids. In addition, certain members of the intestinal microflora la- and 7j8-dehydroxylate primary bile acids yielding deoxycholic acid and lithocholic acid (Fig. 1). Moreover, 3-sulfated bile acids are converted into a variety of different metabolites by the intestinal microflora [6,7]. 

The epimerizalion of the 7a-hydroxyl group can occur either by intra- or interspecies mechanisms [16]. However, it is difficult to quantitatively assess the degree of 7-hydroxy epimerization in vivo because this transformation competes with the irreversible 7-dehydroxylation of bile acids (Section VI). 7a-HSDH activity has been reported in several genera of intestinal bacteria however, the most complete characterization of this enzyme has been carried out with the enzyme isolated from Escherichia coli [37] and Bacteroides sp. [29,38,39] (Table 2). Both enzymes used both free and conjugated bile acids as substrates, showed alkaline pH optima and lower values for dihydroxy than for trihydroxy bile acids. However, cell extracts prepared from Bacteriodes sp. contained both NAD- and NADP-depen-dent 7 -HSDH activities whereas, extracts from E. coli contained only an NAD-de-pendent enzyme activity. Additional studies showed that the two 7a-HSDH activities detected in Bacteriodes sp. differed in molecular weight, differential heat inactivation and Mn " requirement, suggesting the presence of two distinct enzymes [29]. 

The 7)8 epimers of cholic and chenodeoxycholic acid are frequently detected in feces and bile of man. However, the epimerization of the 7)8-hydroxy bile acids by... 

Dried bile from the Himalayan bear (Yutan) has been used for centuries in China to treat liver disease. UDCA (ursodiol, Actigall) is a hydrophilic, dehydroxylated bile acid that is formed by epimerization of the bile acid, chenodeoxycholic acid (CDCA Chenodiol), in the gut by intestinal bacteria. It comprises approximately 1 to 3% of the total bile acid pool in human beings but is present at much higher concentrations in bears. When administered orally, litholytic bile acids, such as chenodiol and ursodiol, can alter relative concentrations of bile acids, decrease biliary lipid secretion, and reduce the cholesterol content of the bile so that it is less lithogenic. Ursodiol also may have cytoprotective effects on hepatocytes and effects on the immune system that account for some of its beneficial effects in cholestatic liver diseases. 

The changes of the cholesterol molecule that occur in its conversion into bile acids include epimerization of the 3 -hydroxyl group, reduction of the double bond, introduction of hydroxyl groups in positions C-7 (cheno-deoxycholic acid), C-7 and C-12 (cholic acid), or C-6 and C-7 (a- and P-muricholic acids, hyocholic acid), and transformation of the C27 side chain into a C24-carboxylic acid. 

Preferential esterification. Startg. tricarboxylic acid and Amberlyst 15 in methanol stirred at room temp, for 10 h monomethyl ester. Y 80%. a,p-Unsatd. and ar. carboxyl groups were left unaffected the method failed with higher alcohols (/-PrOH /-BuOH). Under these mild conditions, a-epimerization, c/5-tra 5-rearrangement, and transesterification (of ethyl esters) are avoided, and keto and olefinic groups remain intact. F.e. inch methyl esters of bile acids s. M. Petrini et al., Synth. Commun. 18, 847-53 (1988). 

Bile acid methyl esters with unprotected hydroxy groups are best separated on QF-1 columns (Table XIII). It is advisable to use 3 % columns since it is often difficult to prepare 0.5-1 % QF-1 columns that do not give tailing of polar compounds. This difficulty has also been experienced by Okishio and Nair (24) who therefore developed a column having a mixture of QF-1, SE-30, and NGS as stationary phase. On QF-1 columns epimeric alchohols... 

The term steroid ( oid being a suffix implying similarity) was coined by Fieser and Fieser (21) to mean a compound that (as with cholesterol (1), its epimeric dihydro derivatives, cholestanol (2) and coprostanol (3), and the bile acids - e.g.. 

The newly born infant gut contents include a complex mixture of neutral and acidic steroids generally present as glycine and taurine conjugates or as sulphates[4]. The pattern of bile acids in meconium probably represents the accumulation of maternal and foetal products and is dominated by cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid and hyocholic acid[5]. Epimeric, unsaturated or side-chain shortened bile acids have also been detected in meconium[6]. This bile acid profile is rapidly lost in infants and, at 18 months, the principle bile acids excreted are cholic acid and... 

Bile acids may be degraded in vitro by intestinal bacteria via a number of pathways including deconjugation, desulphation, dehydroxyl-ation, oxidoreduction, epimerization and dehydrogenation of the steroid nuclus (Figure 2). 

The bioeynthesis of bile acids takes place in the liver. It begins with the insertion of a To-hy-droxyl group into cholesterol the ring is then reduced and epimerized at C-3 (the ketone must be assumed to be the intermediate). After these changes in the ring system, and occasionally after... 

B.a. are biosynthesized from cholesterol by 7a-hy-droxylation, reduction of the double bond at podtion S, and epimerization at position 3. The side chain is shortened by -oxidation. Free B.a. can be prepared by alkaline hydrolysis of animal bile. They are used as starting materials for the partial laboratory synthesis of important steroid hormones. See Cholic acid, Deoxychohc acid, Lithocholic add. 

Alkaline hydrolysis of fresh hog bile provides access to 3a-hydroxy-6-oxo-5a-cholanoic acid (about 3 g/1.5 liter of bile) (92, 93, 13). Figure 11 summarizes the routes to the four epimeric 3,6-diols from this acid. Kawa-nami (94) has studied the susceptibility of the hydroxyl groups of this series to NBS and concludes the following 6 3 (a)>3/S(e)>6a(e). Corbellini et al. (95, 96) and Ziegler (97) have investigated interconversions of isomers at Cg through the mesylates and tosylates. 

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