Metabolic pathways of bile acid synthesis

Elliott, William H.; Hyde, Paul M.

doi:10.1016/0002-9343(71)90281-6

Cited by 70 publications

(21 citation statements)

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“…In a recent study, Wu et al (39) reported significantly elevated blood pressure in rats that were treated orally with CA for one month. However, the primary bile acid CA is converted to DCA by bacteria-mediated 7␣-dehydroxylation in the intestine, reabsorbed in the ileum and transported back to the liver via the portal circulation (40,41). Thus, oral administration of CA may result in increased concentrations of DCA in the circulation, leading to inhibition of 11␤HSD2.…”

Section: Table III Cortisol-induced Nuclear Translocation Of Mr Mediamentioning

confidence: 99%

Chenodeoxycholic Acid and Deoxycholic Acid Inhibit 11β-Hydroxysteroid Dehydrogenase Type 2 and Cause Cortisol-induced Transcriptional Activation of the Mineralocorticoid Receptor

Stauffer

Rochat

Dick

et al. 2002

Journal of Biological Chemistry

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Inappropriate activation of the mineralocorticoid receptor (MR) results in renal sodium retention and potassium loss in patients with liver cirrhosis. Recent evidence suggested that this MR activation is, at least in part, a result of bile acid-dependent reduction in 11␤-hydroxysteroid dehydrogenase type 2 (11␤HSD2) activity, an enzyme preventing cortisol-dependent activation of MR by converting cortisol to cortisone. Here, we investigated the molecular mechanisms underlying bile acid-mediated MR activation. Analysis of urinary bile acids from 12 patients with biliary obstruction revealed highly elevated concentrations of chenodeoxycholic acid (CDCA), cholic acid (CA), and deoxycholic acid (DCA), with average concentrations of 50 -80 M. Although CDCA and DCA both mediated nuclear translocation of MR in the absence of 11␤HSD2 and steroids in transiently expressing HEK-293 cells, the transcriptional activity of MR was not stimulated. In contrast, CDCA and DCA both inhibited 11␤HSD2 with IC 50 values of 22 and 38 M, respectively and caused cortisol-dependent nuclear translocation and increased transcriptional activity of MR. LCA, the bile acid that most efficiently inhibited 11␤HSD2, was present at very low concentrations in cholestatic patients, whereas the weak inhibitor CA did not cause MR activation. In conclusion, these findings indicate that CDCA, and to a lesser extent DCA, by inhibiting 11␤HSD2, mediate cortisol-dependent nuclear translocation and transcriptional activation of MR and are responsible at least for a part of the sodium retention and potassium excretion observed in patients with biliary obstruction.

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Section: Table III Cortisol-induced Nuclear Translocation Of Mr Mediamentioning

confidence: 99%

Chenodeoxycholic Acid and Deoxycholic Acid Inhibit 11β-Hydroxysteroid Dehydrogenase Type 2 and Cause Cortisol-induced Transcriptional Activation of the Mineralocorticoid Receptor

Stauffer

Rochat

Dick

et al. 2002

Journal of Biological Chemistry

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“…1). The first begins with hydroxylation of carbon-26 followed by oxidation to a carboxylic acid and cleavage of the three-carbon fragment as propionic acid (1,2).…”

Section: Introductionmentioning

confidence: 99%

Bile acid synthesis in man. In vivo activity of the 25-hydroxylation pathway.

Duane¹,

Pooler²,

Hamilton³

1988

J. Clin. Invest.

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During biosynthesis of bile acid, carbons 25-26-27 are removed from the cholesterol side-chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the threecarbon fragment is released as acetone. We have previously shown in the rat that the contribution of the 25-hydroxylation pathway can be quantitated in vivo by measuring production of

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“…Since this change occurs simultaneously with the onset of spermiation, it is likely that the same steroid responsible for spermiation is also responsible for pheromone synthesis and release. In addition, P reception is involved in cholesterol regulation (Cahill, 2007), and bile acids such as sea lamprey pheromones are synthesized from cholesterol (Elliott and Hyde, 1971;Javitt, 1994;Russell and Setchell, 1992;Salen and Shefer, 1983). Furthermore, the high level of serum bile acids in patients with intrahepatic cholestasis of pregnancy was associated with high levels of serum and urinary mono-and disulphated P metabolites (Abu-Hayyeh et al, 2013;Laatikainen and Karjalainen, 1973;Meng et al, 1997;Reyes and Sjovaall, 2000;Sjovall and Sjovall, 1970).…”

Section: Discussionmentioning

confidence: 99%