Publications

• Purification and properties of prostaglandin 9-ketoreductase from pig and human kidney. Identity with human carbonyl reductase.

  Schieber A., Frank R.W., Ghisla S.

  Prostaglandin 9-ketoreductase (PG-9-KR) was purified from pig kidney to homogeneity, as judged by SDS/PAGE using an improved procedure. The enzyme is pro-S stereoselective with regard to hydrogen transfer from NADPH with prostaglandin E2 as substrate and reduces its 9-keto group with approximately ... >> More

  Prostaglandin 9-ketoreductase (PG-9-KR) was purified from pig kidney to homogeneity, as judged by SDS/PAGE using an improved procedure. The enzyme is pro-S stereoselective with regard to hydrogen transfer from NADPH with prostaglandin E2 as substrate and reduces its 9-keto group with approximately 90% stereoselectivity to form prostaglandin F2 alpha. Approximately 8% of the prostaglandin F formed has the beta-configuration. In addition to catalyzing the interconversion of prostaglandin E2 to F2 alpha, PG-9-KR also oxidizes prostaglandin E2, F2 alpha and D2 to their corresponding, biologically inactive, 15-keto metabolites. Incubation of PG-9-KR with prostaglandin F2 alpha and NAD+ leads to the preferential formation of 15-keto prostaglandin F2 alpha rather than prostaglandin E2. This suggests that the prostaglandin E2/prostaglandin F2 alpha ratio is not determined by the NADP+/NADPH redox couple. The enzyme also reduces various other carbonyl compounds (e.g. 9,10-phenanthrenequinone) with high efficiency. The catalytic properties measured for PG-9-KR suggest that its in vivo function is unlikely to be to catalyze formation of prostaglandin F2 alpha. The monomeric enzyme has a molecular mass of 32 kDa and exists as four isoforms, as judged by isoelectric focusing. PG-9-KR contains 1.9 mol Zn2+/mol enzyme and no other cofactors. Human kidney PG-9-KR was also purified to homogeneity. The human enzyme has a molecular mass of 34 kDa and also exists as four isoforms. Polyclonal antibodies raised against pig kidney PG-9-KR cross-react with human kidney PG-9-KR and also with human brain carbonyl reductase, as demonstrated by Western blot analysis. Sequence data of tryptic peptides from pig kidney PG-9-KR show greater than 90% identity with human placenta carbonyl reductase. From comparison of several properties (catalytical, structural and immunological properties), it is concluded that PG-9-KR and carbonyl reductase are identical enzymes. << Less

  Eur. J. Biochem. 206:491-502(1992) [PubMed] [EuropePMC]

  This publication is cited by 6 other entries.

• An NADP-linked prostaglandin D dehydrogenase in swine brain.

  Watanabe K., Shimizu T., Iguchi S., Wakatsuka H., Hayashi M., Hayaishi O.

  An NADP-linked 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin D2 was discovered and partially purified from cytosol of swine brain. Prostaglandins A2, B2, D3, E2, and F2 alpha were poor substrates for this enzyme, the rates of reaction being less than 10% of that with prostagland ... >> More

  An NADP-linked 15-hydroxyprostaglandin dehydrogenase specific for prostaglandin D2 was discovered and partially purified from cytosol of swine brain. Prostaglandins A2, B2, D3, E2, and F2 alpha were poor substrates for this enzyme, the rates of reaction being less than 10% of that with prostaglandin D2. The enzyme was separated by Sephadex column chromatography from the other NADP-linked 15-hydroxyprostaglandin dehydrogenase that was also present in brain and metabolized prostaglandins B2, E2, and F2 alpha much more effectively than D2. The primary reaction product was tentatively identified as 15-ketoprostaglandin D2 by its characteristic absorption spectrum with a peak at 415 nm at pH 9. This compound was further converted to 13,14-dihydro-15-ketoprostaglandin D2 in the presence of NADPH by the action of 15-ketoprostaglandin delta 13-reductase that was co-purified with the dehydrogenase. This dehydrogenase appears to be responsible for the specific inactivation of prostaglandin D2 which is the major prostaglandin in the central nervous system. << Less

  J Biol Chem 255:1779-1782(1980) [PubMed] [EuropePMC]