Stereospecific conversion of prostaglandin D2 to (5Z,13E)-(15S)-9 alpha-11 beta,15-trihydroxyprosta-5,13-dien-1-oic acid (9 alpha,11 beta-prostaglandin F2) and of prostaglandin H2 to prostaglandin F2 alpha by bovine lung prostaglandin F synthase.
A prostaglandin F (PGF) synthase was recently purified from bovine lung that catalyzed the reduction of both PGH2 and PGD2 but at different active sites on the enzyme. In view of the recent finding that PGD2 is stereospecifically reduced to a unique biologically active compound, (5Z, 13E)-(15S)-9 alpha, 11 beta, 15-trihydroxyprosta-5,13-dien-1-oic acid (9 alpha,11 beta-PGF2 or 11-epi-PGF2 alpha), by a human liver cytosolic enzyme, detailed characterization of the products formed from PGH2 and PGD2 by the bovine lung PGF synthase was carried out. Chromatographic characteristics of the products formed and stereochemical analysis procedures using mass spectrometry indicated that the enzyme stereospecifically reduces PGH2 to PGF2 alpha, whereas PGD2 is stereospecifically converted to 9 alpha,11 beta-PGF2. The finding that this enzyme catalyzes the formation of both C-11 hydroxy epimers of PGF2, albeit from different substrates, is of interest in that these two compounds may exert different biological actions.
Watanabe
K
K
Iguchi
Y
Y
Iguchi
S
S
Arai
Y
Y
Hayaishi
O
O
Roberts
L J
LJ
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D008168:Lung / Q000201:enzymology; D008968:Molecular Conformation; D015230:Prostaglandin D2; D011449:Prostaglandin Endoperoxides / Q000378:metabolism*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000378:metabolism*; D044262:Prostaglandin H2; D011457:Prostaglandins D / Q000378:metabolism*; D011460:Prostaglandins F / Q000096:biosynthesis*; D011463:Prostaglandins H / Q000378:metabolism*; D013379:Substrate Specificity
D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011457:Prostaglandins D; D011460:Prostaglandins F; D011463:Prostaglandins H; D044262:Prostaglandin H2; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; D015230:Prostaglandin D2