Bile acid conjugation

Bile acid conjugates la 376 Bile acid methyl esters lb 446,448 Binding agent, influence on staining la 123 S-Bioallethrine la 359... 

In addition, three types of lipophilic conjugates have been found in pyrethroid metabolism studies (Fig. 4). They are cholesterol ester (fenvalerate) [15], glyceride (3-PBacid, a common metabolite of several pyrethroids) [16], and bile acid conjugates (fluvalinate) [17]. It is noteworthy that one isomer out of the four chiral isomers of fenvalerate yields a cholesterol ester conjugate from its acid moiety [15]. This chiral-specific formation of the cholesterol ester has been demonstrated to be mediated by transesterification reactions of carboxylesterase(s) in microsomes, not by any of the three known biosynthetic pathways of endogenous cholesterol esters... 

Therapeutic Anti-cancer Use of Bile Acid Conjugates... 

Tolle-Sander S, Lentz KA, Maeda DY, Coop A, Polli JW. Increased acyclovir oral bioavailability via a bile acid conjugate. Mol Pharm 2004 l(l) 40-48. 

Although bile acid conjugates with amino acids are normally excreted into bile, amino acid conjugates of xenobiotics are usually excreted into urine. Conjugation with endogenous amino acids facilitates urinary excretion because of the organic anion transport systems located in the kidney tubules. 

The taurine residue can also be found as an amide derivative of the 26-carboxylic acid function in the 3p,5a,6p,15a-polyhydroxylated steroids 328 and 329, which were obtained from the starfish Myxoderma platyacanthum [245]. The structures of both compounds were determined from spectral data and chemical correlations. The bile of the sunfish Mola mola has been shown to contain a new bile acid conjugated with taurine (330) together with sodium taurocholate. Compound 330 was identified as sodium 2-[3a,7a, 11 a-trihydroxy-24-oxo-5P-cholan-24-yl]amino]ethane-sulfonate on the basis of its physicochemical data and chemical transformations [246]. 

The ability of the series to induce beta-galactosidase transgene expression in COS-7 cells was measured and compared with Lipofectin (quaternary ammonium salt lipid). The transfection activity of the bile acid conjugates ranged from low (38%) in product 2c to 1000% in product 4c, as compared to Lipofectin , which was ranked as 100%. The in vitro success of these unusual cationic facial amphiphiles is inspiring for the development of more efficient chemical methods based on tissue/cell targeting enabled by the polar face of the amphiphile. 

Zelcer N, Reid G, Wielinga P, Kuil A, van der Heijden I, Schuetz JD, Borst P. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J 2003 371 361-367. 

The usefulness of low-energy MS/MS has been shown in the diagnosis of metabolic diseases by analysis of underivatized bile acids, conjugated or not, in complex biological samples such as urine or serum. A series of neutral loss and precursor ion scans was... 

In addition to bile acid conjugation, a variety of other compounds may also be excreted as taurine conjugates, including retinoic acid (Section 2.2.1.3) and a number of xenobiotics. 

To aid hepato-cellular uptake of antisense ODNs, the phosphoramidites of cholic and taurocholic acids were prepared and added to the 5 -end of antisense oligomers." The oligonucleotides were further modified by the inclusion of phosphorothioate and benzylphosphonate internucleotide linkages. The bile acid conjugated oligomers exhibited enhanced lipophilicity as determined by HPLC, and when incorporated into duplexes no destabilisation was observed. An antisense phosphorothioate ODN targeted to the HIV-1 gag-mKNA was... 

Hardison, W. G-, and Grundy, S. M. l 83). tffcci of bile acid conjugation pattern on bile acid metabolism in normal humans. GusfrOfMffwtogy 84, 617-620. 

Several mechanisms have been proposed to explain the cholestasis that occurs during parenteral nutrition, but there is little direct evidence to support any of them. Nutrient deficiencies that may be critical for hepatic uptake, biotransformation, and secretion of bile may be involved. Deficiency of taurine, which is important for bile acid conjugation, may cause cholestasis in premature infants. Certain amino acids may act as toxins. Reduced... 

Bile acid conjugation with a xenobiotic acid Is a recently discovered metabolic pathway ( 8 ). An anlllno acid from the pyrethrold Insecticide fluvallnate acylates the 3-posltlon of natural bile acids In rats ( 85), chickens (86). and a cow (.87), and these conjugates represent 5-12X of the C-resldue In feces (Figure 14). Eight different bile acids have been shown to conjugate with this anlllno acid In these animal species, but so far no other xenobiotic acids have been reported to follow a similar pathway. 

Figure 14. Bile acid conjugates of an anlllno acid.

Around one-quarter of the bile acid conjugates reaching the ileum have the amino acid moiety removed by the action of bacterial enzymes. A decon-jugating enzyme, choloylglycine hydrolase (EC 3.5.1.24) has been isolated from clostridial bacteria (Nl) and is used in methods for the analysis of bile acids. The majority of deconjugated bile acids are reabsorbed and return to the liver, where they are efficiently reconjugated with glycine or taurine (V7). 

The liver, and also bacteria in the small and large intestine, can cause other structural modifications to bile acids as they undergo their entero-hepatic cycle. The formation of sulfate esters, already mentioned with respect to lithocholate in Section 4.2.1, is carried out primarily in the liver in man by a sulfotransferase (Lll). Other bile acids can also be sulfoconjugated to a small extent, mainly at the 3a-hydroxyl position. Bacteria, which have been isolated anaerobically from human feces, are known to possess bile acid sulfatase activity, which removes the 3a-sul te group of chenodeoxycholic and cholic acids (H24). The action of this bacterial enzyme probably explains why only trace amounts of sul ted bile acids, which are poorly absorbed in the intestine, are detected in the feces (12). Another type of bile acid conjugate, which has been identified in the urine of healthy subjects and patients with hepatobiliary disease, is the glucuronide (A7, S41). Both the liver and extrahepatic tissues, such as the kidney and small intestinal mucosa, are capable of glucuronidation of bile acids in man (M14). 

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