Lithocholate

It has been claimed that the elimination of tosylates of 3a-alcohols in 5jS-series gives 3-oleflns with high selectivity. However, the homogeneity of these products is questionable, in view of recent findings concerning the ehmination of 3-chloro compounds (see below) and Fieser s results with the elimination of methyl lithocholate tosylate (ref. 232, cf. ref. 233). Neutral alumina may also be used to effect elimination of tosylates of 3j5-alcohols if the alumina is pretreated with potassium hydroxide the inverted alcohol is the predominant product. 

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... 

Lithocholic add costs 2 or 3 times more than cholesterol. Thus, although the yields are slightly lower with cholesterol, it is cheaper to use it Furthermore, cholesterol is more widely available and in greater quantities than lithocholic add. These two factors tend to favour the use of cholesterol. Lithocholic add does have the advantages, however, of being more water soluble and is, therefore, more easily supplied to cultures in aqueous media. The costs of recovery of die desired product from the reaction brew are also commercially important. The point we are making in this in-text activity is that in selecting a substrate we need to consider more than simply the conversion effidency and the cost of the substrate. 

A medium containing bile salts such as lithocholic add along with carbohydrates and peptone has been used to isolate gut organisms. One such isolate has been shown to completely degrade the lithocholic add (structure given in Figure 9.1). 

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. 

Glutathione S transferases bind bile acids in vitro but doubt has been cast over whether this happens in vivo as these enzymes were not labelled by fluorescently labelled bile acids in experiments to identify the carrier proteins but may play a role with the raised levels in cholestasis. Liver fatty-acid-binding protein has been shown to bind bile acids by using a displacement assay with fluorescent fatty-acid ligand. This work clearly showed displacement to be directly related to hydrophobicity, such that lithocholate conjugates had the greatest effect. This may indicate a mechanism to minimise toxicity within the hepatocyte. 

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. 

Abbreviations used for bile acids in Tables 3.1-3.6 DOC (deoxycholate), LC (lithocholate), CDOC (chenodeoxycholate), C (cholate), GDOC (glycodeoxycholate), TDOC (taurodeoxy-cholate), GCDOC (glycochenodeoxycholate), TCDOC (taurochenodeoxycholate), GC (gly-cocholate), TC (taurocholate). 

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. ... 

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