scholarly journals Human liver class I alcohol dehydrogenaseγγ isozyme: the sole cytosolic 3β-hydroxysteroid dehydrogenase of iso bile acids

Hepatology ◽  
2000 ◽  
Vol 31 (4) ◽  
pp. 990-996 ◽  
Author(s):  
Hanns-Ulrich Marschall ◽  
Udo C.I. Oppermann ◽  
Stefan Svensson ◽  
Erik Nordling ◽  
Bengt Persson ◽  
...  
Keyword(s):  
Bile Acids ◽  
Human Liver ◽  
Hydroxysteroid Dehydrogenase ◽  
Class I

Hepatic reduction of the secondary bile acid 7-oxolithocholic acid is mediated by 11β-hydroxysteroid dehydrogenase 1

2011 ◽  
Vol 436 (3) ◽  
pp. 621-629 ◽  
Author(s):  
Alex Odermatt ◽  
Thierry Da Cunha ◽  
Carlos A. Penno ◽  
Charlie Chandsawangbhuwana ◽  
Christian Reichert ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Human Liver ◽  
Liver Microsomes ◽  
Three Dimensional ◽  
Hydroxysteroid Dehydrogenase ◽  
Binding Mode ◽  
Bile Acid Metabolism ◽  
Secondary Bile Acid ◽  
Micro Organisms

The oxidized bile acid 7-oxoLCA (7-oxolithocholic acid), formed primarily by gut micro-organisms, is reduced in human liver to CDCA (chenodeoxycholic acid) and, to a lesser extent, UDCA (ursodeoxycholic acid). The enzyme(s) responsible remained unknown. Using human liver microsomes, we observed enhanced 7-oxoLCA reduction in the presence of detergent. The reaction was dependent on NADPH and stimulated by glucose 6-phosphate, suggesting localization of the enzyme in the ER (endoplasmic reticulum) and dependence on NADPH-generating H6PDH (hexose-6-phosphate dehydrogenase). Using recombinant human 11β-HSD1 (11β-hydroxysteroid dehydrogenase 1), we demonstrate efficient conversion of 7-oxoLCA into CDCA and, to a lesser extent, UDCA. Unlike the reversible metabolism of glucocorticoids, 11β-HSD1 mediated solely 7-oxo reduction of 7-oxoLCA and its taurine and glycine conjugates. Furthermore, we investigated the interference of bile acids with 11β-HSD1-dependent interconversion of glucocorticoids. 7-OxoLCA and its conjugates preferentially inhibited cortisone reduction, and CDCA and its conjugates inhibited cortisol oxidation. Three-dimensional modelling provided an explanation for the binding mode and selectivity of the bile acids studied. The results reveal that 11β-HSD1 is responsible for 7-oxoLCA reduction in humans, providing a further link between hepatic glucocorticoid activation and bile acid metabolism. These findings also suggest the need for animal and clinical studies to explore whether inhibition of 11β-HSD1 to reduce cortisol levels would also lead to an accumulation of 7-oxoLCA, thereby potentially affecting bile acid-mediated functions.

Human liver ADH γγ-isoenzyme is the sole cytosolic 3β-hydroxysteroid dehydrogenase of iso-bile acids

1998 ◽  
Vol 28 ◽  
pp. 126 ◽  
Author(s):  
HU Marschall ◽  
U Oppermann ◽  
S Svensson ◽  
B Persson ◽  
JO Höög ◽  
...  
Keyword(s):  
Bile Acids ◽  
Human Liver ◽  
Hydroxysteroid Dehydrogenase

scholarly journals Structural and functional comparison of two human liver dihydrodiol dehydrogenases associated with 3 α-hydroxysteroid dehydrogenase activity

1992 ◽  
Vol 282 (3) ◽  
pp. 741-746 ◽  
Author(s):  
Y Deyashiki ◽  
H Taniguchi ◽  
T Amano ◽  
T Nakayama ◽  
A Hara ◽  
...  
Keyword(s):  
Bile Acids ◽  
Dehydrogenase Activity ◽  
Human Liver ◽  
Hydrogen Transfer ◽  
Peptide Mapping ◽  
Reductase Activity ◽  
High Specificity ◽  
Hydroxysteroid Dehydrogenase ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Two monomeric dihydrodiol dehydrogenases with pI values of 5.4 and 7.6 were co-purified with androsterone dehydrogenase activity to homogeneity from human liver. The two enzymes differed from each other on peptide mapping and in their heat-stabilities; with respect to the latter the dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activities of the respective enzymes were similarly inactivated. The pI 5.4 enzyme was equally active towards trans- and cis-benzene dihydrodiols, and towards (S)- and (R)-forms of indan-1-ol and 1,2,3,4-tetrahydronaphth-1-ol and oxidized the 3 alpha-hydroxy group of C19-, C21- and C24-steroids, whereas the pI 7.6 enzyme showed high specificity for trans-benzene dihydrodiol, (S)-forms of the alicyclic alcohols and C19- and C21-steroids. Although the two enzymes reduced various xenobiotic carbonyl compounds and the 3-oxo group of C19- and C21-steroids, and were A-specific in the hydrogen transfer from NADPH, only the pI 5.4 enzyme showed reductase activity towards 7 alpha-hydroxy-5 beta-cholestan-3-one and dehydrolithocholic acid. The affinity of the two enzymes for the steroidal substrates was higher than that for the xenobiotic substrates. The two enzymes also showed different susceptibilities to the inhibition by anti-inflammatory drugs and bile acids. Whereas the pI-5.4 enzyme was highly sensitive to anti-inflammatory steroids, showing mixed-type inhibitions with respect to indan-1-ol and androsterone, the pI 7.6 enzyme was inhibited more potently by non-steroidal anti-inflammatory drugs and bile acids than by the steroidal drugs, and the inhibitions were all competitive. These structural and functional differences suggest that the two enzymes are 3 alpha-hydroxysteroid dehydrogenase isoenzymes.

Class III human liver alcohol dehydrogenase: a novel structural type equidistantly related to the class I and class II enzymes

Biochemistry ◽  
1988 ◽  
Vol 27 (4) ◽  
pp. 1132-1140 ◽  
Author(s):  
Rudolf Kaiser ◽  
Barton Holmquist ◽  
John Hempel ◽  
Bert L. Vallee ◽  
Hans Jörnvall
Keyword(s):  
Alcohol Dehydrogenase ◽  
Human Liver ◽  
Structural Type ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Liver Alcohol Dehydrogenase

scholarly journals Inhibition of 11?-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

Hepatology ◽  
1999 ◽  
Vol 30 (3) ◽  
pp. 623-629 ◽  
Author(s):  
Daniel Ackermann ◽  
Bruno Vogt ◽  
Genevi�ve Escher ◽  
Bernhard Dick ◽  
J�rg Reichen ◽  
...  
Keyword(s):  
Bile Acids ◽  
Hydroxysteroid Dehydrogenase

Effect of protein on the determination of total bile acids in serum.

1983 ◽  
Vol 29 (1) ◽  
pp. 171-175 ◽  
Author(s):  
N Q Hanson ◽  
E F Freier
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Hydroxysteroid Dehydrogenase ◽  
Inhibitory Effect ◽  
Normal Serum ◽  
Total Serum ◽  
Enzyme Preparations ◽  
Analytical Recovery ◽  
Fluorescence Light

Abstract We measured total serum bile acids on a fluorescence-light-scattering micro centrifugal analyzer by the direct enzymatic method with 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) and with resazurin as a fluorogenic electron acceptor. We found that serum protein has an inhibitory effect on the measurement of bile acids, but this effect was eliminated by adding bovine serum albumin to the reaction mixture in a final protein concentration (12.2 g/L) that was high compared with that contributed by a normal serum specimen. The assay is a sensitive method that reaches equilibrium in 5 min. The method is microscale (5 microL of sample, 150 microL of working reagent), is easy to perform, and is accurate (analytical recovery = 104.1%) and precise (CV = 11.1 and 5.7% on specimens with bile acid concentrations of 7.6 and 35.4 mumol/L, respectively). Normal values are 1-12 and less than 9 mumol/L on nonfasting and fasting individuals, respectively. Pure 3 alpha-hydroxysteroid dehydrogenase must be used: we found several enzyme preparations that gave falsely high values for bile acid.

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