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

Abstract：

: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 Km value toward tiaprofenic acid than the cytosol (Km = 164 ± 18 μM vs. 569 ± 74 μM, respectively), whereas the cytosol showed higher specific activity during reduction than the microsomes (Vmax = 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.

journal_name

Chem Biol Interact

journal_title

Chemico-biological interactions

authors

Malátková P,Skarka A,Musilová K,Wsól V

doi

10.1016/j.cbi.2017.03.006

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

121-126

eissn

0009-2797

issn

1872-7786

pii

S0009-2797(17)30303-4

journal_volume

276

pub_type

杂志文章

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