Journal
JOURNAL OF BIOCHEMISTRY
Volume 145, Issue 2, Pages 161-168Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvn152
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science Postdoctoral Fellowship [02271]
- Takeda Foundation
- Fondation pour la Recherche Medicale
- Osaka City
Ask authors/readers for more resources
Here, we show that three enzymes belonging to the 1B group of the aldoketo reductase (AKR) superfamily, i.e., human placental aldose reductase (AKR1B1), mouse kidney aldose reductase (AKR1B3) and mouse vas deferens protein (AKR1B7), catalyse the reduction of prostaglandin (PG) H-2, a common intermediate of various prostanoids, to form PGF(2) in the presence of NADPH. AKR1B1, AKR1B3 and AKR1B7 displayed higher affinities for PGH(2) (K-m 1.9, 9.3 and 3.8 M, respectively) and V-max values (26, 53 and 44 nmol/min/mg protein, respectively) than did the human lung PGF(2) synthase (AKR1C3; 18 M and 4 nmol/min/mg protein, respectively). The PGF(2) synthase activity of AKR1B1 and AKR1B3 was efficiently inhibited by two AKR inhibitors, tolrestat (K-i 3.6 and 0.26 M, respectively) and sorbinil (K-i 21.7 and 0.89 M, respectively), in a non-competitive or mixed-type manner, whereas that of AKR1B7 was not sensitive to these inhibitors (K-i 9.2 and 18 mM, respectively). These data provide a molecular basis for investigating novel functional roles for AKR1B members and PGF(2) as mediators of physiological and pathological processes in mammalian organisms.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available