Reductive metabolism of tiaprofenic acid by the human liver and recombinant carbonyl reducing enzymes

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10365694" target="_blank" >RIV/00216208:11160/17:10365694 - isvavai.cz</a>
Result on the web
<a href="http://www.sciencedirect.com/science/article/pii/S0009279717303034" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0009279717303034</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cbi.2017.03.006" target="_blank" >10.1016/j.cbi.2017.03.006</a>

Result language
angličtina
Original language name
Reductive metabolism of tiaprofenic acid by the human liver and recombinant carbonyl reducing enzymes
Original language description
Tiaprofenic acid is a widely used anti-inflammatory drug; however, the reductive metabolism of tiaprofenic acid is not yet well understood. Here, we compared the reduction of tiaprofenic acid in microsomes and cytosol from the human liver. The microsomes exhibited lower K-m value toward tiaprofenic acid than the cytosol (K-m = 164 +/- 18 mu M vs. 569 +/- 74 mu M, respectively), whereas the cytosol showed higher specific activity during reduction than the microsomes (V-max = 728 +/- 52 pmol mg of protein(-1) min(-1) vs. 285 +/- 11 pmol mg of protein(-1) min(-1), respectively). Next, a panel of recombinant carbonyl reducing enzymes from AKR and SDR superfamilies has been studied to find the enzymes responsible for the cytosolic reduction of tiaprofenic acid. CBR1 was identified as the reductase of tiaprofenic acid with high specific activity (56,965 +/- 6741 pmol mg of protein(-1) min(-1)). Three other enzymes, AKR1A1, AKR1B10, and AKR1C4, were also able to reduce tiaprofenic acid, but with very low activity. Thus, CBR1 was shown to be a tiaprofenic acid reductase in vitro and was also suggested to be the principal tiaprofenic acid reductase in vivo.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy

Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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