Prostaglandin F2 Synthase Activities of AldoKeto Reductase 1B1, 1B3 and 1B7

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.