Nitric oxide donors activate the cyclo-oxygenase and peroxidase activities of prostaglandin H synthase.
Prostaglandin H synthase (PHS) is a dual enzyme with cyclo-oxygenase and peroxidase activities. The nitric oxide (NO) donors, sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP) and spermine NONOate (SPER/NO), activated both cyclo-oxygenase and peroxidase activities of PHS. SNP activated PHS by increasing Vmax without affecting Km, the activation constants being 1.0 mM for cyclo-oxygenase and 1.3 mM for peroxidase. Analysis of progress curves and absorption spectra of PHS suggested that NO released from SNP interacted with the heme at the active site of the enzyme. Moreover, SNP counteracted the peroxide-induced inactivation of PHS, suggesting that the interplay between the intracellular peroxide and NO is critical in tuning PHS activity in cells.
Maccarrone
M
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Italy.
Putti
S
S
Finazzi Agrò
A
A
D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009589:Nitrogen Oxides; C091861:spermine nitric oxide complex; D009599:Nitroprusside; D013096:Spermine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases; D010396:Penicillamine