Degradation bile acid chains

Additional applications are exemplified by the well-known Meystre-Miescher degradation of the bile acid side chain and, more recently, in the preparation of a-pyrones from a,iS-unsaturated lactones. ... 

Bjorkemd, I., 1992, Mechanism of degradation ofthe steroid side chain in the formation of bile acids, 7. Lipid Res. 33 455-471. 

MIESCHER DEGRADATION. Adaptation of the Barbier-Wieland carboxylic acid degradation to pcrmil simultaneous elimination of three carbon atoms, as in degradation of the bile acid side chain to the methyl ketone stage. Conversion of the methyl ester of the bile acid to the tertiary alcohol, followed by dehydration, bromination. dehydrohalogenatinn, and oxidation of the diene yields die required degraded ketone. 

A method for the degradation of the side chain of bile acids or lanosterol has been described.178 Cholanic acid or lithocholic acid were first converted into the phenyl... 

Two pathways have been proposed for degradation of the cholestane side chain in the biosynthesis of bile acids. These differ in the site proposed for the first hydroxylation step in side-chain oxidation and are discussed below for the formation of cholic add. 

Decarboxylation /-Butylhydroperoxide. Copper powder. Dimethyl sulfoxide. Iron. Decarboxylation, oxidative Lead dioxide. Lead tetraacetate. Pyridine-N-oxide. Degradation, bile acid side chain Periodic acid. 

In 1971, Makino et al. found that considerable amounts of 3jS-hydroxychol-5-en-24-oic acid were excreted in urine of children with extrahepatic biliary atresia [111]. Since then, the unsaturated C24 bile acid has been identified in human meconium [112,113], amniotic fluid [114,115], gallbladder bile from premature and term infants [116], urine from children and adults, both healthy and with liver disease [82,117], and bile and feces from newborn and fetal guinea pigs [118]. The natural occurrence of 3j8-hydroxychol-5-en-24-oic acid suggests that the side chain of cholesterol is degraded before modification of the steroid ring system (Chapter 9). 

Danielsson and Kazuno have shown that 5j8-ranol is an efficient precursor of cholic acid in bile fistula rats while 26-deoxy-5)S-ranol is not [134]. The mechanism of the side-chain degradation of 5 -ranol is not known but probably an oxidation of the 26-hydroxyl group to a carboxyl group followed by a /S-oxidation. 

Baes, M., Huyghe, S., Carmeliet, P., Declercq, P. E., Collen, D., Mannaerts, G. P., and Van Veldhoven, P. P. Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J Biol Chem 275 (2000) 16329-16336. 

Degradation of bile acid side chains to methyl ketones... 

Degradation of the bile acid side chain. Fetizon et al. have described a convenient new procedure for degradation of the side chains of bile acids and lanosterol. The method is illustrated for methyl cholanate (1). The first steps ... 

Schematically shown are two separate P-oxidation systems, one involved in degradation of straight chain fatty acid derivatives (left side), the other handling 2-melhyl-branched compounds (right side), each of them consisting of four steps that are catalyzed by an acyl-CoA oxidase, a multifimctional protein (MFP) (containing two or more activities) and a thiolase. Only the proteins belonging to the left system are (at least in rodents) induced by peroxisome proliferators and correspond to those initially discovered and characterized in rat liver. In rat, the CoA-esters of bile acid intermediates and pristanic acid are desaturated by separate enzymes (highlighted in italie), while in man only one oxidase appears to be involved. Before the naturally occurring 2R-pristanic acid and 25R-bile acid intermediates can be desaturated, a racemisation reaction is required. The 2-methyl-2-enoyl-CoAs, generated by the oxidases, are thought to be hydrated by the same MFP-2. Under normal conditions, the intermediates are believed to be channeled from...

As discussed above, the peroxisomal fatty acid P-oxidation system is specifically involved in the degradation of a specific group of fatty acids including very-long-chain fatty acids, pristanic acid and di- and trihydroxycholestanoic acid. Several inherited diseases in man have been described in which peroxisomal P-oxidationis impaired at some level as reflected in the differential acciunulation of very-long-chain fatty acids, pristanic acid and the bile acid intermediates in plasma from patients. The following disorders can be distinguished ... 

The degradation of the bile acid side chain is best carried out (Mattox and Kendall, 1950) at the 1 l-keto-12a-bromo oxide stage (VI), since... 

A second problem of great current interest has to do with the microbial degradation of the side chains of cholesterol and related sterols. In 1948, Turfitt (T-1034) observed that Proactinomyces erthropolis degraded cholestenone and bile acids to a very minor degree to the corresponding etio acids. No further transformations of... 

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