Biotransformation of ursodeoxycholic acid by Pseudomonas sp

Abstract

The metabolism of ursodeoxycholic acid by Pseudomonas sp NCIB 10590 has been studied in phosphate-buffered mineral salts. The organism completely metabolized ursodeoxycholic acid in 24 hr, and time-course experiments revealed that maximum product formation occurred at 14 hr. The major products detected and identified at 14 hr were 78-hydroxychol4-en-3-one-24-oic acid, 7~-hydroxy-3-oxo-pregna-l,4-diene-20carboxylic acid, and 78-hydroxyandrosta-l,4-diene-3,17-dione. Several minor intermediates were isolated and evidence is given for the following structures: 7~-hydroxy-5~-cholan-3-oxo-24-oic acid, 78-hydroxyandmt-4-en-3,17-dione, 7/3,178-dhyhxyandrvstarosta1,4-diene-3-one, 3-hydroxy-1,3,5(10)-9,lO-seco-androstatriene-3,17dione-78-01, and 22a-hydroxymethylpregna-1,4-diene-3-one-7j3-ol. -Owen, R. W., R. Wait, and R. E Baton. Biotransformation of ursodeoxycholic acid by Pseudomonas sp NCIB 10590. J. Lipid Res. 1988. 29: 459-468. Supplementary key words mass spectrometry infrared spectrophotometry bile acids nuclear magnetic resonance Ursodeoxycholic acid (UDCA) is a major biliary bile acid of some species of bears (1) and has also been detected in human bile (2) and feces (3). The pharmacology of UDCA has been described in detail (4, 5) because it is now used as a drug for the dissolution of radiolucent gallstones in man. When UDCA is orally administered to man, the bile becomes enriched with UDCA so that it may represent up to 60% of biliary bile acids (5). The mechanism of action of UDCA may rely, in part, on being transformed to chenodeoxycholic acid (CDCA) which is also used for the dissolution of gallstones (6-8). However, due to side effects of CDCA treatment, UDCA is now the drug of choice. UDCA may be converted to CDCA during the enterohepatic circulation; that which is not absorbed in the terminal ileum enters the colon where it is subjected to two types of bacterial enzymic attack. UDCA can be oxidized by 76-hydroxysteroid dehydrogenase (76-HSDH) to give 3a-hydroxy-5~-7-oxo-cholanoic acid (7KLA) which can be reduced to CDCA either by the colonic flora (9) or by cytochrome P450-mediated hepatic enzymes (10) after passive absorption from the colon. UDCA can also be dehydroxylated by colpnic bacteria to lithocholic acid which is subsequently excreted in feces (11). The use of UDCA as a chemotherapeutic drug has led many research groups to study the metabolism of this bile acid by bacteria. Much of the work so far has concentrated on the metabolism of UDCA by bacteria indigenous to the human intestinal tract. Macdonald et al. (12) have shown that UDCA can be converted to CDCA via 7KLA by Clostridium absonum; this epimerization reaction is substantiated by several other studies (13, 14). UDCA is also known to be epimerized at C3; this is demonstrated in twenty species of Clostridium perfringens by Hirano et al. (15). To date there is no evidence for extensive metabolism of UDCA by bacteria. Hence a study has been conducted on the biotransformation of UDCA by Pseudomonas sp NCIB 10590 (Pseudomonas sp 10590).

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Cite this paper

@inproceedings{Owen2002BiotransformationOU, title={Biotransformation of ursodeoxycholic acid by Pseudomonas sp}, author={W. Geoffrey Owen and R. Wait and Rodney F . Biltont}, year={2002} }