Acids cholic acid

Yamashita et al. [82] added up to 10 mM taurocholic acid, cholic acid (cmc 2.5 mM), or sodium laurel sulfate (SLS low ionic strength cmc 8.2 mM) to the donating solutions in Caco-2 assays. The two bile acids did not interfere in the transport of dexamethasone. However, SLS caused the Caco-2 cell junctions to become leakier, even at the sub-CMC 1 mM level. Also, the permeability of dexamethasone decreased at 10 mM SLS. 

The two most important bile acids, cholic acid C24H40Os and desoxy-cholic acid C24H40O4, occur in ox bile in combination, partly with glycine and partly with taurine as glyco- and taurocholic and glyco- and tauro-desoxycholic acids. The linkage between the amino acids and the bile acids is of an amide nature. On hydrolysis the nitrogenous constituents are split off. 

In contrast, the fluorescence spectra of the parent y-cyclodextrins (compounds y-CD1, y-CD2, y-CD3, y-CD4) exhibit both monomer and excimer bands in the absence of guests because the cavity is large enough to accommodate both fluorophores (Figure 10.38). The ratio of excimer and monomer bands changes upon guest inclusion. The ratio of the intensities of the monomer and excimer bands was used for detecting various cyclic alcohols and steroids (cyclohexanol, cyclo-dodecanol, i-borneol, 1-adamantanecarboxylic acid, cholic acid, deoxycholic acid and parent molecules, etc.). 

Contrasting with rodents, BAT is found in small amounts in adult humans. It has been proposed that skeletal muscle rather than BAT may play a pivotal role in energy homeostasis in adult humans. The authors also demonstrated that cultured human skeletal muscle myoblasts express D2 and high levels of TGR5, and a number of common bile acids (cholic acid, taurocholic acid, deoxycholic acid, chenodeoxycholic acid) were able to increase cAMP levels concomitant with increased D2 activity (Figure 7.4). Taurocholic acid was also able to... 

Hydroxylation, shortening of the hydrocarbon chain, and addition of a carboxyl group convert cholesterol in a complex series of reactions to the bile acids, cholic acid, and chenodeoxycholic acid. 

CMPA, CE MEKC CSP e.g. cyclodextrins, amino acids cholic acids, tartaric acids, alkaloids etc. and Derivatives Thereof analytical to preparative excellent, fair to moderate... 

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... 

Dansyl-modified (3-CD dimer (63) shows interesting molecular recognition ability for bile acids [55], It gives very different AI/I0 values, as shown by 0.54, 0.21, 0, and 0.03 for ursodeoxycholic acid, chenodeoxycholic acid, cholic acid, and deoxycholic acid, respectively, under the conditions of 2 pM for the host and 0.3 mM for the guests. The binding constants of 6.9 X 103 and 1.3 X 103 M 1 were obtained for ursodeoxycholic acid and chenodeoxycholic acid, respectively, on the basis of 1 1 stoichiometry. 

Scalia and Games developed a packed column SFC method for the analysis of free bile acids cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) [32]. The baseline separation of all five bile acids was achieved on a packed phenyl column with a methanol-modified carbon dioxide in less than 4 min. The elution order showed a normal-phase mechanism because the solutes eluted in the order of increasing polarity following the number of hydroxyl groups on the steroid nucleus. The method was also applied to the assay of UDCA and CDCA in capsule and tablet formulations. The method was found to be linear in the range 1.5-7.5 ng/ml (r > 0.99, n = 6). The average recoveries (n= 10) for UDCA and CDCA were 100.2% with a RSD of 1.7% and 101.5% with a RSD of 2.2%, respectively. The reproducibility of the method was less than 1.5% (n = 10) for both UDCA and CDCA. 

Bile Acids, Sterols, and Steryl Esters Many of these compounds have high melting points, making them unsuitable for melt applications. Exceptions are the salicylic acid-cholic acid system formed by a melt-granulation technique reported by Froemming and Vetter.f The system provided a sustained release in acid media (pH 1-3.5). 

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 ... 

Bile acids are found, as their name suggests, in bile, which is formed in the liver and then stored in the gall bladder. Of these acids, cholic acid (41) is the most abundant. A structural feature which cholic acid shares with the other bile acids is a cis a/b ring fusion, which is seen in the structure of 41. 

The bile acids are 24-carbon steroid derivatives. The two primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the hepatocytes from cholesterol by hy-droxylation, reduction, and side chain oxidation. They are conjugated by amide linkage to glycine or taurine before they are secreted into the bile (see cholesterol metabolism. Chapter 19). The mechanism of secretion of bile acids across the canalicular membrane is poorly understood. Bile acids are present as anions at the pH of the bile, and above a certain concentration (critical micellar concentration) they form polyanionic molecular aggregates, or micelles (Chapter 11). The critical micellar concentration for each bile acid and the size of the aggregates are affected by the concentration of Na+ and other electrolytes and of cholesterol and lecithin. Thus, bile consists of mixed micelles of conjugated bile acids, cholesterol, and lecithin. While the excretion of osmotically active bile acids is a primary determinant of water and solute transport across the canalicular membrane, in the canaliculi they contribute relatively little to osmotic activity because their anions aggregate to form micelles. 

The bile acids cholic acid and chenodeoxycholic acid are synthesized from cholesterol in the liver (Dl, S3). Several structural modifications are necessary to convert cholesterol, with its 27 carbon atoms, C-5,6 double bond and 3p-hydroxyl group, to a 24-carbon atom, saturated, 3,7 and 12a-hydroxyl-ated bile acid. The major reactions in this transformation are shown in Figs. 3 and 4. The reactions are catalyzed by mitochondrial, microsomal, soluble, and possibly peroxisomal enzymes. 

The two bile acids, cholic acid and chenodeoxycholic acid, which are synthesized from cholesterol in the liver, are termed primary bile acids. Each day, around one-third to one-quarter of the primary bile acid pool is lost or converted to secondary bile acids by anaerobic bacteria in the intestine. This is achieved by 7a-dehydroxylation, a process which converts cholic acid to deoxycholic acid (3a,12a-dihydroxy-5p-cholan-24-oic acid) and chenodeoxycholic acid into lithocholic acid (3a-hydroxy-5 -cholan-24-oic acid). 

Synthesis of the Bile Acid Cholic Acid (a) and the Bile Salt Glycocholate (b). 

Fig. 1. Comparison of structures of 5a- and 5/8-bile acids. Allocholic acid (3a,7a,12a-trihydroxy-5a-cholanic acid) cholic acid (3a,7a,12a-trihydroxy-5 -cholanic acid).

A study of the reduction of [24- C]3-oxo-5j8-cholanic acid in bile fistula rats given [l- Hjjethanol showed that all metabolites had a 3a-hydroxy group and all radioactive products (lithocholate, 3a,6/8-dihydroxy-5 -cholanate, chenodeoxycho-late and y8-muricholate) contained about 13 atom% excess deuterium in the 3/9 position. Thus, the 3)8-hydroxy-5/9-steroid dehydrogenase isoenzyme of alcohol dehydrogenase [172] has no function in the reductive metabolism of bile acids. Cholic acid was not radioactive but contained deuterium at the 3)8, 5)8 and other positions, probably because of the transfer of deuterium from ethanol via NADH to NADPH, which it utilized in the biosynthesis of cholesterol and bile acids and in oxido reduction of the 3-hydroxyl group of the latter [173]. 

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]. 

Another hydroxylation role for vitamin C in the hepatic microsomal fraction is the stepwise conversion of cholesterol to the bile acid, cholic acid, via 7a-hydroxycholesterol, 3a,7a-dihydroxycoprostane and 3a,7a,12o-trihydroxycoprostane. Also, in lipid metabolism, conventional fatty acids with an even number of carbon atoms are a-oxidised by a mono-oxygenase and subsequently decarboxylated to form an odd-numbered carbon derivative and both these steps appear to require ascorbic acid. As the initial a-oxidation is brought about by a... 

Biliary Acids.—The bile of most animals contains the sodium salts of two amido-acids of complex constitution. These acids may be decomposed into a non-nitrogenized acid (cholic acid), and either an amido-acid (glyco-col), or au amido-sulphuroua acid (taurine). The following biliary acids have been described ... 

Amino Acids Cholic Acid Sodium Palmitate Palmitic Acid Linoleic Acid Cholestrol Cholestrol Acetate Cholesterol Palmitate Lecithin Tripalmitin... 

There are species differences for the individual bile acids. Cholic acid is the major primary bile acid in most species. Muricholic acid is a major bile acid in the rat that increases rapidly during cholestasis (Hofmann 1988). More experimental work is needed to analyze the patterns of individual bile acids after various forms of chemically induced liver injury to see if these profiles can provide better diagnosis. 

It is considered that the motion of guest molecules depends on the space sizes even at the same temperature. That is, the molecules can move more freely in a larger space than in a smaller space. Such a difference would affect polymerization behaviors. Such space effects can be observed on the basis of subtle changes of polymerization behaviors by using a suitable set of hosts. Use of a set of the hosts, deoxycholic acid, apocholic acid, cholic acid, and chenodeoxycholic acid, enables us to observe the effects of one-dimensional polymerization in detail. On the other hand, a pair composed of urea and thiourea is not suitable for such an aim, because the pair does not include identical monomers at the same temperatures. 

Various bile salts have effects on the hydrolysis rate that do not parallel their effect on the lowering of surface tension. Thus RotUin and Schalch (303) found the order of stimulation of lipase hydrolysis was cholic acid > taurocholic acid > deoxycholic acid, but the order for maximum decrease of surface tension was deoxycholic acid > taurocholic acid > cholic acid. Kawashima (304) found that chohc acid increased the synthetic activity of pancreatic lipase to a greater extent than did deoxycholic acid, and that bile itself was far more effective than chohe acid. The special efficiency of bile was assumed to be due to the presence of amino acids. 

Fig. 1. The two 24-carbon primary bile acids in man are I, 3a,7a,12a-trihydroxy-5/5-cho]anoic acid (cholic acid), and II, 3a,7a-dihydroxy-5iS-cholanoic acid (chenodeoxycholic acid). Their immediate precursors are, respectively. III, 3a,7a,12a-trihydroxy-5/3-cholestanoic acid, and IV, 3a,7a-dihydroxy-5jS-cholestanoic acid.

---