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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

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1437-4315
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Volume 400, Issue 5

Issues

Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1

Linbing Fan
  • School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin 30072, China
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/ Jan Felix Joseph
  • Freie Universitaet Berlin, Institute of Pharmacy, Pharmaceutical and Medicinal Chemistry (Pharmaceutical Analyses), Berlin, Germany
  • Freie Universitaet Berlin, Department of Biology, Chemistry, Pharmacy, Core Facility BioSupraMol, Berlin, Germany
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/ Pradeepraj Durairaj
  • School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin 30072, China
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/ Maria Kristina Parr
  • Freie Universitaet Berlin, Institute of Pharmacy, Pharmaceutical and Medicinal Chemistry (Pharmaceutical Analyses), Berlin, Germany
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/ Matthias Bureik
  • Corresponding author
  • School of Pharmaceutical Science and Technology, Health Sciences Platform, Tianjin University, Tianjin 30072, China
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Published Online: 2018-12-18 | DOI: https://doi.org/10.1515/hsz-2018-0379

Abstract

The human cytochrome P450 enzyme CYP8B1 is a crucial regulator of the balance of cholic acid (CA) and chenodeoxycholic acid (CDCA) in the liver. It was previously shown to catalyze the conversion of 7α-hydroxycholest-4-en-3-one, a CDCA precursor, to 7α,12α-dihydroxycholest-4-en-3-one, which is an intermediate of CA biosynthesis. In this study we demonstrate that CYP8B1 can also convert CDCA itself to CA. We also show that five derivatives of luciferin are metabolized by CYP8B1 and established a rapid and convenient inhibitor test system. In this way we were able to identify four new CYP8B1 inhibitors, which are aminobenzotriazole, exemestane, ketoconazole and letrozole.

This article offers supplementary material which is provided at the end of the article.

Keywords: bile acid; cytochrome P450; fission yeast; liver; S. pombe; steroid hydroxylation

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About the article

Received: 2018-09-19

Accepted: 2018-11-13

Published Online: 2018-12-18

Published in Print: 2019-04-24


Citation Information: Biological Chemistry, Volume 400, Issue 5, Pages 625–628, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2018-0379.

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