Prostaglandin F₂α Synthase Activities of Aldo-Keto Reductase 1B1, 1B3 and 1B7

• Published in: Journal of biochemistry (Tokyo) 2009-02, Vol.145 (2), p.161-168
• Main Authors: Kabututu, Zakayi, Manin, Michèle, Pointud, Jean-Christophe, Maruyama, Toshihiko, Nagata, Nanae, Lambert, Sarah, Lefrançois-Martinez, Anne-Marie, Martinez, Antoine, Urade, Yoshihiro
• Format: Article
• Language: English
• Subjects: prostaglandin F2α; prostaglandin H2; prostaglandin H2 F2α-reductase; sorbinil; tolrestat
• ISSN: 0021-924X; 1756-2651
• DOI: 10.1093/jb/mvn152

Here, we show that three enzymes belonging to the 1B group of the aldo-keto 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) H₂, a common intermediate of various prostanoids, to form PGF₂α in the presence of NADPH. AKR1B1, AKR1B3 and AKR1B7 displayed higher affinities for PGH₂ (Km = 1.9, 9.3 and 3.8 μM, respectively) and Vmax values (26, 53 and 44 nmol/min/mg protein, respectively) than did the human lung PGF₂α synthase (AKR1C3; 18 μM and 4 nmol/min/mg protein, respectively). The PGF₂α synthase activity of AKR1B1 and AKR1B3 was efficiently inhibited by two AKR inhibitors, tolrestat (Ki = 3.6 and 0.26 μM, respectively) and sorbinil (Ki = 21.7 and 0.89 μM, respectively), in a non-competitive or mixed-type manner, whereas that of AKR1B7 was not sensitive to these inhibitors (Ki = 9.2 and 18 mM, respectively). These data provide a molecular basis for investigating novel functional roles for AKR1B members and PGF₂α as mediators of physiological and pathological processes in mammalian organisms.