Peroxidation in position C-6 of progesterone-3-ethanolimine is increased by the presence of enzymes generating oxygen radicals.
The generation of 6-oxygenated (6 beta-hydroxy, 6 beta-hydroperoxy, and 6-oxo) progesterone derivatives during the hydrolysis of progesterone-3-ethanolimine has been shown to be increased in the presence of xanthine/xanthine oxidase. The combination of xanthine/xanthine oxidase with other enzymes and/or reagents that catalyze transformation (or formation) of oxygen radicals suggested that the most likely oxygen species participating in the 6-oxygenation was the protonated acid of the superoxide anion, i.e., the hydroperoxy radical. The suggestion was further supported by experiments with oxygen scavengers. However, the data presented do not rule out a radical propagation reaction since the steroid compound used may be more reactive than the scavengers tested. A stimulation of 6-oxygenation of progesterone-3-ethanolimine by NADPH-supplemented rat liver microsomes was found. This reaction was inhibited by the only oxygen scavenger (reduced glutathione) found to be effective in the xanthine/xanthine oxidase experiments. The similarities between the two oxygenation systems may implicate a mechanism for 6 beta-hydroperoxidation of 3-oxo-4-ene steroids in rat liver microsomes.
Eriksson
C G
CG
Department of Clinical Chemistry and Blood Coagulation, Karolinska Hospital, Stockholm, Sweden.
Eneroth
P
P
D000818:Animals; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000494:pharmacology; D006868:Hydrolysis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011374:Progesterone / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D026082:Singlet Oxygen; D013481:Superoxides / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D005290:Ferric Compounds; D005296:Ferrous Compounds; D005609:Free Radicals; D014970:Xanthines; D013481:Superoxides; C066181:progesterone-3-ethanolimine; D026082:Singlet Oxygen; D019820:Xanthine; D011374:Progesterone; D009249:NADP; D014969:Xanthine Oxidase; D005978:Glutathione; D010100:Oxygen