Hepatic metabolism of short-chain bile acids. Inversion of the 3-hydroxyl group of isoetianic acid (3β-hydroxy-5β-androstane-17β-carboxylic acid) by the adult rat

J. M. Little, J. S. Pyrek, A. Radominska, Karen Shattuck, R. Lester

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The stereospecificity of mechanisms for hepatic transport of short-chain bile acids has been examined by following the hepatic metabolism and biliary secretion of 3β-hydroxy-5β-androstane-17β-carboxylic acid (isoetianic acid) administered in two different labeled forms to rats prepared with an external biliary fistula. While 93% of the administered [2,2,4,4- 3H]isoetianic acid was recovered in bile after 20 h, only 18% of a similar dose of [3α-3H]isoetianic acid was secreted in bile over the same time period. The recovered radioactivity of the latter compound was mainly associated with bile water. With the [2,2,4,4-3H]isoetianic acid, the bulk of the biliary isotope was determined to be in the form of two glucuronide conjugates. Spectral analysis identified these metabolites as the hydroxyl- linked (major) and carboxyl-linked (minor) β-glucuronides, not of the 3β- hydroxy compound administered, but of 3α-hydroxy-5β-androstane-17β- carboxylic acid (etianic acid), i.e., the products of hydroxyl group inversion. It is concluded that isoetianic acid is efficiently cleared from plasma and conjugated with glucuronic acid after its epimerization to etianic acid. The prevalent, but not complete, loss of the 3-tritium atom and the retention of the 2- and 4-tritium atoms probably indicates a 3-oxo-5β- androstane-17β-carboxylic acid intermediate with partial return of the label via a limited labeled pool of reduced nicotinamide cofactor.

Original languageEnglish (US)
Pages (from-to)1949-1957
Number of pages9
JournalJournal of Lipid Research
Volume32
Issue number12
StatePublished - 1991
Externally publishedYes

Fingerprint

Carboxylic Acids
Bile Acids and Salts
Metabolism
Hydroxyl Radical
Rats
Bile
Liver
Tritium
Glucuronides
Biliary Fistula
Cutaneous Fistula
Atoms
Glucuronic Acid
Niacinamide
Radioactivity
Metabolites
Isotopes
Spectrum analysis
Labels
androstane

Keywords

  • biliary secretion
  • epimerization
  • glucuronide conjugates

ASJC Scopus subject areas

  • Endocrinology

Cite this

Hepatic metabolism of short-chain bile acids. Inversion of the 3-hydroxyl group of isoetianic acid (3β-hydroxy-5β-androstane-17β-carboxylic acid) by the adult rat. / Little, J. M.; Pyrek, J. S.; Radominska, A.; Shattuck, Karen; Lester, R.

In: Journal of Lipid Research, Vol. 32, No. 12, 1991, p. 1949-1957.

Research output: Contribution to journalArticle

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abstract = "The stereospecificity of mechanisms for hepatic transport of short-chain bile acids has been examined by following the hepatic metabolism and biliary secretion of 3β-hydroxy-5β-androstane-17β-carboxylic acid (isoetianic acid) administered in two different labeled forms to rats prepared with an external biliary fistula. While 93{\%} of the administered [2,2,4,4- 3H]isoetianic acid was recovered in bile after 20 h, only 18{\%} of a similar dose of [3α-3H]isoetianic acid was secreted in bile over the same time period. The recovered radioactivity of the latter compound was mainly associated with bile water. With the [2,2,4,4-3H]isoetianic acid, the bulk of the biliary isotope was determined to be in the form of two glucuronide conjugates. Spectral analysis identified these metabolites as the hydroxyl- linked (major) and carboxyl-linked (minor) β-glucuronides, not of the 3β- hydroxy compound administered, but of 3α-hydroxy-5β-androstane-17β- carboxylic acid (etianic acid), i.e., the products of hydroxyl group inversion. It is concluded that isoetianic acid is efficiently cleared from plasma and conjugated with glucuronic acid after its epimerization to etianic acid. The prevalent, but not complete, loss of the 3-tritium atom and the retention of the 2- and 4-tritium atoms probably indicates a 3-oxo-5β- androstane-17β-carboxylic acid intermediate with partial return of the label via a limited labeled pool of reduced nicotinamide cofactor.",
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AB - The stereospecificity of mechanisms for hepatic transport of short-chain bile acids has been examined by following the hepatic metabolism and biliary secretion of 3β-hydroxy-5β-androstane-17β-carboxylic acid (isoetianic acid) administered in two different labeled forms to rats prepared with an external biliary fistula. While 93% of the administered [2,2,4,4- 3H]isoetianic acid was recovered in bile after 20 h, only 18% of a similar dose of [3α-3H]isoetianic acid was secreted in bile over the same time period. The recovered radioactivity of the latter compound was mainly associated with bile water. With the [2,2,4,4-3H]isoetianic acid, the bulk of the biliary isotope was determined to be in the form of two glucuronide conjugates. Spectral analysis identified these metabolites as the hydroxyl- linked (major) and carboxyl-linked (minor) β-glucuronides, not of the 3β- hydroxy compound administered, but of 3α-hydroxy-5β-androstane-17β- carboxylic acid (etianic acid), i.e., the products of hydroxyl group inversion. It is concluded that isoetianic acid is efficiently cleared from plasma and conjugated with glucuronic acid after its epimerization to etianic acid. The prevalent, but not complete, loss of the 3-tritium atom and the retention of the 2- and 4-tritium atoms probably indicates a 3-oxo-5β- androstane-17β-carboxylic acid intermediate with partial return of the label via a limited labeled pool of reduced nicotinamide cofactor.

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