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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemico-Biological Interactions

ISSN

0009-2797

e-ISSN

—

Svazek periodika

276

Číslo periodika v rámci svazku

October

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

6

Strana od-do

121-126

Kód UT WoS článku

000416215800017

EID výsledku v databázi Scopus

2-s2.0-85017105374