A free radical mediated cooxidation of tetramethylhydrazine by prostaglandin hydroperoxidase.
Prostaglandin endoperoxide synthase catalyzed the oxidation of tetramethylhydrazine to the tetramethylhydrazine radical cation, as detected by electron spin resonance spectroscopy. Oxidation of tetramethylhydrazine by prostaglandin endoperoxide synthase also resulted in the N-demethylation of tetramethylhydrazine leading to the formation of formaldehyde. Both the radical and formaldehyde formation were dependent on arachidonic acid, inhibited by indomethacin, and supported by 15-hydroperoxyarachidonic acid, indicating that the metabolism was peroxidative. We propose that tetramethylhydrazine undergoes two sequential one-electron oxidations yielding an iminium cation, which is then hydrolyzed to yield formaldehyde. Metabolism of hydrazines by prostaglandin endoperoxide synthase may be of importance in tissue containing low mixed-function oxidase activity.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005557:Formaldehyde / Q000378:metabolism; D005609:Free Radicals; D008297:Male; D008763:Methylhydrazines / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep
D002273:Carcinogens; D005609:Free Radicals; D008763:Methylhydrazines; D005557:Formaldehyde; C013705:tetramethylhydrazine; C022464:prostaglandin hydroperoxidase; D010544:Peroxidases; D011451:Prostaglandin-Endoperoxide Synthases