Taurocholic acid

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. 

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. 

Taupunkt, m. dew point thaw point. Taurochol-salz, n. taurocholate. -saure, / taurocholic acid. 

L-Cysteine is a precursor of the thioethanolamine portion of coenzyme A and of the taurine that conjugates with bile acids such as taurocholic acid (Chapter 26). 

The thioethanolamine of coenTyme A and the taurine of taurocholic acid arise from cysteine. 

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. 

These general observations have been confirmed in PAMPA measurements in our laboratory, using the 2% DOPC-dodecane lipid. With very lipophilic molecules, glycocholic acid added to the donor solution slightly reduced permeabilities, taurocholic acid increased permeabilities, but SLS arrested membrane transport altogether in several cases (especially cationic, surface-active drugs such as CPZ). 

Bile salt export pump (BSEP gene symbol ABCB11) mediates the biliary excretion of nonconjugated bile salts, such as taurocholic acid, glycocholic acid and cholic acid, and therefore is responsible for the formation of the bile acid-dependent bile flow [97, 98]. Its hereditary defect results in the acquisition of PFIC2, a potentially lethal disease which requires liver transplantation [17, 81, 82, 99]. As discussed in Section 12.5.2, the inhibition of BSEP following drug administration may result in cholestasis. 

TC7 Caco-2 subclone High taurocholic acid transport Stable expression of CYP3A4 Expression of CYP3A5 Low expression of P-gp... 

OATP2B1 (old name OATP-B) is expressed at brush-border membranes of intestinal epithelial cells [32], OATP2B1 exhibited pH-sensitive transport activities for various organic anions such as estrone-3-sulfate, dehydroepiandros-terone sulfate, taurocholic acid, pravastatin, and fexofenadine [33], However, further studies are needed to determine the specific physiological and pharmacokinetic contribution of OATP2B1 for intestinal absorption of these compounds. 

Woodcock, S., Williamson, I., Hassan, I., and Mackay, M., Isolation and characterization of clones from the Caco-2 cell line displaying increased taurocholic acid transport, ]. Cell Sci., 98, 323, 1991. 

A related protein, MRP3, has similar structure to this mutated MRP2 and can transport taurocholic acid but mutation of the equivalent residue, leucine 1084, with lysine-blocked transport of taurocholic acid. In cholestasis there is an induction of MRP3 mRNA suggesting that this transporter is active, at least when bile-acid concentrations are raised within the hepatocyte. This transporter function is shown in Figure 2.1. 

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... 

Jones, K. A. and Kara, T. J. (1982). Behavioral response by Arctic chart (Salvelinus alpinus) to taurocholic acid and L-serine, two putative semio-chemicals. American Zoologist 22, 925. 

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). 

Gelissen, I. C., and M. A. Eastwood. Taurocholic acid adsorption during non-starch polysaccharide fermentation an in vitro study. Brit J Nutr 1995 74(2) 221-228. 

Does Citrus Pectin Bind Bile Salts A possible mechanism by which dietary pectin may cause lowering of cholesterol levels in rats has been reported (1 9). In these in vitro studies, pectin was found to inhibit the transport of taurocholic acid from everted sacs of rat intestine. The absorption of labelled cholesterol was depressed by the addition of 5% pectin to the diet as evidenced by increased excretion of labelled cholesterol and diminished cholesterol deposition in the liver. It was concluded from these studies that pectin lowers cholesterol levels in cholesterol-fed rats primarily by binding bile salts and, consequently, by impairing cholesterol absorption. Results similar to those obtained with dietary pectin and described have also been reported for other non-nutritive substances such as guar gum, psyllium seed colloid and seruglucan (20). 

Consequently, absorption enhancers were used in dry powder and liquid formulations to enhance the pulmonary absorption of SCT. Without absorption enhancers, SCT absorption from dry powder or solution was similar to that observed after intratracheal administration. However, the absorption was more improved from dry powder than from solution when absorption enhancers (oleic acid, lecithin, citric acid, taurocholic acid, dimethyl-[5-cyclodextrin, octyl-P-D-glu-coside) were co-administered intratracheally. Such improved absorption could be due to the fact that enhancers added to the dry powder dissolved at high concentration because only a trace volume of fluid lining the alveolar epithelium was available for their dissolution. However, the potential implications of such a mechanism on lung toxicity, especially in lung edema, is yet to be investigated in detail [68]. 

A special consideration in the digestion of fats is that they are not water soluble and cannot be placed in aqueous solution along with the water-soluble lipase digestive enzymes. However, intimate contact is obtained by emulsification of fats through the action of bile salts from glycocholic and taurocholic acids produced from cholesterol in the liver ... 

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