Acid, lithocholic

Problem 27.9 Lithocholic acid is an A-B cis steroid found in human bile. Draw lithocliolic acid showing chair conformations as in Figure 27.11, and tell whether the hydroxyl group at C3 is axial or equatorial. 

Lithocholic acid, structure of, 1082 Locant, IUPAC naming and, 87 Lone-pair electrons, 9 Loratadine, structure of, 206 Lotaustralin. structure of. 766 Low -density polyethylene, synthesis of, 1210... 

The isolate appears to produce the enzymes for the complete catabolism of lithocholic acid. However, in the presence of Pb2+ ions, some of these catabolic enzymes are inhibited, leading to the accumulation of partial breakdown products. It appears that enzymes involved in catabolism of the ring structure are more susceptable to inhibition by Pb2+ ions than are the enzymes involved in side chain catabolism. 

Chenodeoxycholic acid Deoxycholic acid Lithocholic acid Ursodeoxycholic acid Muricholic acid... 

Lipoprotein Metabolism Lipoproteins Liposomes 5-Lipoxygenase Lipoxygenases Lithocholic Acid Local Anaesthetics Locus... 

Although products of fat digestion, including cholesterol, are absorbed in the first 100 cm of small intestine, the primary and secondary bile acids are absorbed almost exclusively in the ileum, and 98—99% are returned to the liver via the portal circulation. This is known as the enterohepatic circulation (Figure 26—6). However, lithocholic acid, because of its insolubility, is not reabsorbed to any significant extent. Only a small fraction of the bile salts escapes absorption and is therefore eliminated in the feces. Nonetheless, this represents a major pathway for the elimination of cholesterol. Each day the small pool of bile acids (about 3-5 g) is cycled through the intestine six to ten times and an amount of bile acid equivalent to that lost in the feces is synthesized from cholesterol, so that a pool of bile acids of constant size is maintained. This is accomplished by a system of feedback controls. 

Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, Mackenzie KI, La-Tour A et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA 2001 98(6) 3 369 3374. 

Coprostanol (50 coprostanol), lithocholic acid, cholest 5 en 7 one 30 ol Manure, faecal deposition [4,47,48,49]... 

Fatty acids have also been converted to difunctional monomers for polyanhydride synthesis by dimerizing the unsaturated erucic or oleic acid to form branched monomers. These monomers are collectively referred to as fatty acid dimers and the polymers are referred to as poly(fatty acid dimer) (PFAD). PFAD (erucic acid dimer) was synthesized by Domb and Maniar (1993) via melt polycondensation and was a liquid at room temperature. Desiring to increase the hydrophobicity of aliphatic polyanhydrides such as PSA without adding aromaticity to the monomers (and thereby increasing the melting point), Teomim and Domb (1999) and Krasko et al. (2002) have synthesized fatty acid terminated PSA. Octanoic, lauric, myristic, stearic, ricinoleic, oleic, linoleic, and lithocholic acid acetate anhydrides were added to the melt polycondensation reactions to obtain the desired terminations. As desired, a dramatic reduction in the erosion rate was obtained (Krasko et al., 2002 Teomim and Domb, 1999). 

They developed a continuum elastic-free energy model that suggests these observations can be explained as a first-order mechanical phase transition. In other recent work on steroids, Terech and co-workers reported the formation of nanotubes in single-component solutions of the elementary bile steroid derivative lithocholic acid, at alkaline pH,164 although these tubules do not show any chiral markings indicating helical aggregation. 

Deconjugation and dehydroxylation reactions occur in the colon, leading to the formation of dozens of new distinct BAs, by the action of the colonic bacteria. The final products enter the enterohepatic circulation and reach the liver where they are reconjugated mostly to either glycine or taurine. Some lithocholic acid, the most toxic substance produced in the body and a known carcinogen, enters the liver where it is sulfated or esterified to glucuronic acid and excreted. 

Bile acids within the enterohepatic circulation that undergo absorption in the terminal ileum encounter a relatively low number of species and population of bacteria and return to the liver in portal blood relatively unchanged. However, the approximately 5% of the bile-acid pool that enters the colon provides substrate for the extensive microbial population that deconjugate and oxidise hydroxyl groups leading to formation of the secondary bile acids deoxycholic and lithocholic acids that are the major bile acids in faeces. 

The interest in bile acids as potential carcinogens was subject to investigation as early as 1940 when Cook et al. reported in Nature that repeated injection of deoxycholic acid into the flanks of mice could induce tumour formation in mice." Furthermore, Kelsey and Pienta showed that treatment of hamster embryo cells with lithocholic acid could cause cell transformation. ... 

Similarly, Kitazawa and colleagues examined the effect of deoxycholic acid (DCA) and lithocholic acid (LCA) during the initiation of rat... 

CA, cholic acid CDCA, chenodeoxycholic acid DCA, deoxycholic acid LCA, lithocholic acid. Tumor end-point also ... 

Figure 5.2 Therapeutic interventions for decreasing colorectal mucosal bile acid exposure as a CRC chemoprevention strategy. 1) Lifestyle modifications including reduction in dietary animal fat and increased fibre intake may, at least partly, be explained by reduction in luminal primary (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary (deoxycholic acid [DCA] and lithocholic acid [LCA]) bile acids. 2) Reduction of secondary bile acids, which are believed to have pro-carcinogenic activity could be obtained by decreased bacterial conversion from primary bile acids. 3) Alternatively, bile acids could be sequestered by chemical binding agents, e.g. aluminium hydroxide (Al(OH)3) or probiotic bacteria. 4) Exogenous ursodeoxycholic acid (UDCA) can reduce the luminal proportion of secondary bile acids and also has direct anti-neoplastic activity on colonocytes in vitro.

P. K. Baijal, D. W. Fitzpatrick and R. P. Bird, Comparative effects of secondary bile acids, deoxycholic and lithocholic acids, on aberrant crypt foci growth in the postinitiation phases of colon carcinogenesis, Nutr. Cancer, 1998, 31, 81. 

B. S. Reddy and K. Watanabe, Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res., 1979, 39, 1521. 

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