Prostaglandin F2[alpha] Synthase Activities of Aldo-Keto Reductase 1B1, 1B3 and 1B7.
Kabututu, Zakayi 1; Manin, Michele 2; Pointud, Jean-Christophe 2; Maruyama, Toshihiko 1; Nagata, Nanae 1; Lambert, Sarah 2; Lefrancois-Martinez, Anne-Marie 2; Martinez, Antoine 2; Urade, Yoshihiro 1,*
[Article] Journal of Biochemistry. 145(2):161-168, February 2009.

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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 PGF2[alpha] in the presence of NADPH. AKR1B1, AKR1B3 and AKR1B7 displayed higher affinities for PGH2 (Km=1.9, 9.3 and 3.8 [mu]M, respectively) and Vmax values (26, 53 and 44 nmol/min/mg protein, respectively) than did the human lung PGF2[alpha] synthase (AKR1C3; 18 [mu]M and 4 nmol/min/mg protein, respectively). The PGF2[alpha] synthase activity of AKR1B1 and AKR1B3 was efficiently inhibited by two AKR inhibitors, tolrestat (Ki=3.6 and 0.26 [mu]M, respectively) and sorbinil (Ki=21.7 and 0.89 [mu]M, 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 PGF2[alpha] as mediators of physiological and pathological processes in mammalian organisms.

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