Constraints on prostaglandin biosynthesis in tissues.
The formation of prostaglandins by prostaglandin H synthase can be limited by the availability of the fatty acid substrate or the hydroperoxide activator and also by a self-catalyzed inactivation associated with the oxygenation reaction. Each pmol of synthase appeared able to form only about 1300 pmol of prostaglandin from arachidonate before it was inactivated. This extent of synthesis was not diminished when substrate fatty acid was complexed with cytosolic proteins even though the velocity of the oxygenation reaction was greatly decreased by the lower availability of substrate acid. When the availability of hydroperoxide activator was decreased by added glutathione peroxidase, the extent of oxygenation per mol of synthase was decreased irrespective of the amount of cytosolic protein present. Approximately 65% of the total prostaglandin synthesis by homogenates was suppressed with a glutathione peroxidase to prostaglandin H synthase ratio of about 90. The remaining prostaglandin synthetic activity was more resistant, being completely suppressed only when the ratio of peroxidase to synthase exceeded 750. The overall ratio of glutathione peroxidase (peroxide-removing) capacity to prostaglandin synthetic (peroxide-forming) capacity in selected tissues ranged from over 1800 in rat liver to less than 30 in leukocytes. A comparison between the daily urinary output of prostaglandin metabolites and tissue prostaglandin synthetic capacity suggested that prostaglandin H synthase inactivation along with glutathione peroxidase suppression of the extent of prostaglandin synthase may be important in limiting prostaglandin biosynthesis within cells.
D000818:Animals; D002460:Cell Line; D005979:Glutathione Peroxidase / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008297:Male; D009928:Organ Specificity; D010101:Oxygen Consumption; D011451:Prostaglandin-Endoperoxide Synthases / Q000302:isolation & purification / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep; D013154:Spleen / Q000201:enzymology
D011453:Prostaglandins; D005979:Glutathione Peroxidase; D011451:Prostaglandin-Endoperoxide Synthases