3 alpha-hydroxysteroid dehydrogenase activity of the Y' bile acid binders in rat liver cytosol. Identification, kinetics, and physiologic significance.

Stolz, Andrew; Takikawa, Hajime; Sugiyama, Yuichi; Kuhlenkamp, John; Kaplowitz, Neil

doi:10.1172/jci112829

Cited by 66 publications

(34 citation statements)

References 31 publications

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“…In hepatocytes, bile acids bind to cytosolic bile acid binding protein, which is a member of the monomeric reductase gene family and has dihydrodiol dehydrogenase activity but does not have activity toward bile acids in human (22). In contrast, the major bile acid binder is identical to 3␣-HSD in rat hepatocytes (23). The bile acid binding protein may assist in the rapid intracellular transport of bile acids from the sinusoidal pole to the canalicular pole of the cell.…”

Section: Discussionmentioning

confidence: 96%

Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

Mano

Sato

Nagata

et al. 2004

Journal of Lipid Research

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We have previously demonstrated that the rat brain contains three unconjugated bile acids, and chenodeoxycholic acid (CDCA) is the most abundantly present in a tight protein binding form. The ratio of CDCA to the other acids in rat brain tissue was significantly higher than the ratio in the peripheral blood, indicating a contribution from either a specific uptake mechanism or a biosynthetic pathway for CDCA in rat brain. In this study, we have demonstrated the existence of an enzymatic activity that converts 3 ␤ -hydroxy-5-cholenoic acid into CDCA in rat brain tissue. To distinguish marked compounds from endogenous related compounds, 18 O-labeled 3 ␤ -hydroxy-5-cholenoic acid, 3 ␤ ,7 ␣ -dihydroxy-5-cholenoic acid, and 7 ␣ -hydroxy-3-oxo-4-cholenoic acid were synthesized as substrates for in vitro incubation studies. The results clearly suggest that 3 ␤ -hydroxy-5-cholenoic acid was converted to 3 ␤ ,7 ␣ -dihydroxy-5-cholenoic acid by microsomal enzymes. The 7 ␣ -hydroxy-3-oxo-4-cholenoic acid was produced from 3 ␤ ,7 ␣ -dihydroxy-5-cholenoic acid by the action of microsomal enzymes, and ⌬ 4 -3-oxo acid was converted to CDCA by cytosolic enzymes. These findings indicate the presence of an enzymatic activity that converts 3 ␤ -hydroxy-5-cholenoic acid into CDCA in rat brain tissue. Furthermore, this synthetic pathway for CDCA may relate to the function of 24 S -hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.

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Section: Discussionmentioning

confidence: 96%

Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

Mano

Sato

Nagata

et al. 2004

Journal of Lipid Research

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“…In the liver, its distinct, high affinity bile acid binding affinity suggests a role in bile acid transport along with steroid metabolism, while in other tissues it may modulate androgen activity. In rat liver, a single rat 3 ␣ -HSD (AKR1C9) is expressed, which has a role in synthesis of primary bile acids from cholesterol as well as sequestration of bile acids within the cytosol (22)(23)(24)(25). Structural analysis of these mammalian HSDs has revealed highly conserved amino acid sequences and a three-dimensional structure consisting of an 8-chain ␣ / ␤ barrel (26,27).…”

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confidence: 99%

A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13

Vergnes

Phan

Stolz

et al. 2003

Journal of Lipid Research

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A subclass of hydroxysteroid dehydrogenases (HSD) are NADP(H)-dependent oxidoreductases that belong to the aldo-keto reductase (AKR) superfamily. They are involved in prereceptor or intracrine steroid modulation, and also act as bile acid-binding proteins. The HSD family members characterized thus far in human and rat have a high degree of protein sequence similarity but exhibit distinct substrate specificity. Here we report the identification of nine murine AKR genes in a cluster on chromosome 13 by a combination of molecular cloning and in silico analysis of this region. These include four previously isolated mouse HSD genes (Akr1c18, Akr1c6, Akr1c12, Akr1c13), the more distantly related Akr1e1, and four novel HSD genes. These genes exhibit highly conserved exon/intron organization and protein sequence predictions indicate 75% amino acid similarity. The previously identified AKR protein active site residues are invariant among all nine proteins, but differences are observed in regions that have been implicated in determining substrate specificity. Differences also occur in tissue expression patterns, with expression of some genes restricted to specific tissues and others expressed at high levels in multiple tissues. Our findings dramatically expand the repertoire of AKR genes and identify unrecognized family members with potential roles in the regulation of steroid metabolism. -Vergnes, L., J. Phan, A. Stolz, and K. Reue. A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13. J. Lipid Res. 2003. 44: 503-511.

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“…Cytosolic CarbonyVquinone reductases include species (and tissue-specific isoforms of prostaglandin dehydrogenases and hydroxysteroid dehydrogenases (3a-HSD, 17P-HSD, 20a-HSD, 20P-HSD isoforms ; as reviewed in Maser, 1995) and, until now, have been grouped either into the aldoketo reductase or short-chain dehydrogenase protein superfamilies (Bohren et al, 1989;Krook et al, 1993a, b;Klein et al, 1992;Bruce et al, 1994). The oxidation of trans-dihydrodiols of ultimate carcinogenic aromatic compounds to their non-carcinogenic catechol metabolites is also mediated by enzymes which belong to the above mentioned groups, and which are often identical to each other, such as cytosolic rat liver 3a-HSDl dihydrodiol dehydrogenase/bile-acid-binding protein (Stolz et al, 1987;Smithgall et al, 1988). Their expression results in a decrease in the mutagenic potential of certain polyaromatic compounds (Glatt et al, 1979;Stolz et al, 1991 ;Pawlowski et al, 1991;Cheng et al, 1991;Klein et al, 1992;Qin et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Cloning and Primary Structure of Murine 11β‐Hydroxysteroid Dehydrogenase/Microsomal Carbonyl Reductase

Oppermann

Netter

Maser

1995

European Journal of Biochemistry

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Screening of a mouse liver Agt 11 cDNA library with a rat liver 1lP-hydroxysteroid dehydrogenase cDNA (11P-HSDrlA) and subsequent screening with an isolated mouse probe, resulted in the isolation and structure determination of a mouse cDNA encoding an amino acid sequence which is very similar to human and rat 11P-hydroxysteroid dehydrogenases (78 % and 86 % similar, respectively), and also to other known vertebrate 1 lP-hydroxysteroid dehydrogenase structures. Open-reading-frame analysis and the deduced amino acid sequence predict a protein with a molecular mass of 32.3 kDa which beIongs to the superfamily of the short-chain dehydrogenase proteins. The amino acid sequence contains two potential glycosylation sites. These data are in agreement with information on the glycoprotein character of the native enzyme. This kind of post-translational modification seems to be a determining factor concerning the equilibrium of the catalyzed llP-dehydrogenation/ll -ox0 reduction step [Obeid,

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3 alpha-hydroxysteroid dehydrogenase activity of the Y' bile acid binders in rat liver cytosol. Identification, kinetics, and physiologic significance.

Cited by 66 publications

References 31 publications

Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems

A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13

Cloning and Primary Structure of Murine 11β‐Hydroxysteroid Dehydrogenase/Microsomal Carbonyl Reductase

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