Metabolism of Prostaglandin D2 by 11-Ketoreductase in the Rabbit Liver
In 1973, Nugteren and Hazelhof  described the formation of PGD2 from endoperoxides (PGG2 and PGH2). Subsequently, PGD2 has been found to be one of the major products of arachidonic acid cascade in many tissue and cell types . Recently, several groups of investigators have demonstrated the transformation of PGH2 to PGD2 in brain homogenates [3, 4] and neuroblastoma cells . The enzyme, PGD2 synthetase, which catalyzed the conversion of PGH2 to PGD2, has been purified to homogeneity and clearly distinguished from that of glutathione-s-transferase . It has been demonstrated that PGD2 is released by platelets during aggregation . PGD2 has also been found to be a potent inhibitor of platelet aggregation, with a potency only less than that of prostacyclin (PGI2) and its stable biologically active metabolite, 6-keto-PGE1 [8, 9]. Although PGD2 is not metabolized by the lung 15-hydroxyprostaglandin dehydrogenase in vitro [10, 11], Ellis and co-workers  have found that over two thirds of the PGD2 metabolite of the monkey have the cyclo-pentane-1,3-diol structure of PGF2α. They suggested that the infused PGD2 may have been converted to PFG2α by a possible enzymic route: 11-Ketoreductase, before it was further metabolized by 15-hydroxyprostaglandin dehydrogenase and β-oxidation. In addition, as early as 1974, Hensby  described the conversion of PGD2 to PGF2α in sheep blood in vitro.
KeywordsRabbit Liver Enzyme Fraction NADPH Generate System Radiometric Assay NADH NADPH
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