- Bile acid transformations by Alcaligenes recti
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Metabolism of cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid by the grown cells of the bacterium Alcaligenes recti suspended in water was studied.Each isolated metabolite was characterized by the application of various spectroscopic methods.Cholic acid, chenodeoxycholic acid, ursodeoxycholic acid, and deoxycholic acid yielded methylated derivatives 3α-methoxy-7α,12α-dihydroxy-5β-cholanoic acid, 3α-methoxy-7α-hydroxy-5β-cholanoic acid, 3α-methoxy-7β-hydroxy-5β-cholanoic acid, and 3α-methoxy-12α-hydroxy-5β-cholanoic acid, respectively.In addition, cholic acid furnished 7α,12α-dihydroxy-3-oxochol-4-en-24-oic acid; chenodeoxycholic acid gave 7α-hydroxy-3-oxo-5β-cholanoic acid and 7α-hydroxy-3-oxochol-4-en-24-oic acid while ursodeoxycholic acid yielded 7β-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid.The formation of various metabolites showed that two competitive enzymic reactions, i.e., selective methylation of the 3α-hydroxy group and dehydrogenation in the A/B rings, were operative.The methylation process was found to be enzymic involving an S-adenosyl-L-methionine (AdoMet)-dependent methyl transferase, and this reaction appeared to be inhibitory to the process of degradation of the ring system.In the other reaction sequence, degradation of the ring system was initiated by dehydrogenation of the 3α-hydroxy group.A 7β-dehydratase activity producing the Δ6 double bond was also noticeable in the metabolism of ursodeoxycholic acid. Keywords: sterols; bile acids; metabolites; microbial transformation; Alcaligenes recti; bacterial transformation
- Mazumder, Ipsita,Mahato, Shashi B.
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- Synthesis of potential C27-intermediates in bile acid biosynthesis and their deuterium-labeled analogs
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In connection with studies of alternative pathways in bile acid biosynthesis, potential intermediates in a pathway starting with 27-hydroxylation of cholesterol have been prepared in natural and deuterated forms. Established methods were used to prepare 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid. Clemmensen reduction of kryptogenin in unlabeled and deuterated solvents yielded 27-hydroxycholesterol and 16-oxo-5-cholestene-3β,27-diol, which were separated by adsorption chromatography on Unisil. The labeled 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid derived from it consisted of molecules with seven (50%), six (20%), and eight (20%) deuterium atoms, and unlabeled molecules were not detected. The acetates of 27-hydroxycholesterol and methyl 3β-hydroxy-5-cholestenoate were 7α-hydroxylated in a copper-catalyzed reaction with ert-butylperbenzoate, and the products were purified by chromatography on Unisil. The 7β-epimers were obtained as side products. Labeled 3β, 7α-dihydroxy-5-cholenic acid was prepared in the same way from 3β-hydroxy-5-[2,2,4,4,23-2H5]-cholenoic acid. The 3-oxo-Δ4 analogs of the 3β-hydroxy-Δ5 compounds were prepared by oxidation with cholesterol oxidase. The labeled products had the same isotopic composition as the starting materials. Gas chromatographic retention indices and mass spectral characteristics of the trimethylsilyl ether derivatives of the neutral steroids and the methylated acids are given for all compounds. (Steroids 58:119-125, 1993).
- Shoda, Junichi,Axelson, Magnus,Sjoevall, Jan
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p. 119 - 125
(2007/10/02)
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- POTENTIAL BILE ACID METABOLITES. X. SYNTHESES OF STEREOISOMERIC 3,7-DIHYDROXY-5α-CHOLANIC ACIDS
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New synthetic routes to allochenodeoxycholic (3α,7α-dihydroxy-5α-cholanic) and alloursodeoxycholic (3α,7β-dihydroxy-5α-cholanic) acids, and their stereoisomers are described.Treatments of allo 7α-hydroxy-3β-tosyloxy ester with N,N-dimethylformamide and of allo 7α-mesyloxy-3β-tosyloxy and 3β-cathyloxy-7α-mesyloxy esters with potassium superoxide-crown ether afforded the desired 3α,7α-, 3α,7β-, and 3β,7β-dihydroxy stereoisomers, respectively, in high yield.Highperformance liquid chromatography was of key importance in characterizing the compounds and determining their purity.Keywords--bile acid; allo bile acid; 3,7-dihydroxy-5α-cholanic acid; allochenodeoxycholic acid; alloursodeoxycholic acid; N,N-dimethylformamide reaction; potassium superoxide-18-crown-6 ether reaction; HPLC
- Iida, Takashi,Momose, Toshiaki,Nambara, Toshio,Chang, Frederic C.
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p. 1929 - 1933
(2007/10/02)
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