An NADP-linked prostaglandin D dehydrogenase in swine brain.

Abstract

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.