Leukotriene C synthetase, a special glutathione S-transferase: properties of the enzyme and inhibitor studies with special reference to the mode of action of U-60,257, a selective inhibitor of leukotriene synthesis.
The cytosolic glutathione S-transferases of rat liver have been fractionated by chromatofocusing into 10 distinct fractions based on their reactivity with 2,4-dinitrochlorobenzene. All these fractions were capable of generating leukotriene C4 (LTC4) from leukotriene A4 (LTA4) to some extent. An inhibitor of leukotriene synthesis, U-60,257, inhibited the activity of these enzymes. The cytosolic glutathione S-transferases of rat basophil leukemia (RBL) cells have been similarly fractionated. U-60,257 inhibited the activity of some of these fractions but not that of others. None of the fractions of the enzyme from RBL cells formed LTC4 from LTA4. The microsomal glutathione S-transferase from rat liver also produced LTC4 from LTA4. It differs from the microsomal LTC synthetase of RBL cells in at least two respects: (1) The enzyme from RBL cells did not react with chromophoric substrates like dinitrochlorobenzene while the enzyme from liver did react. (2) Triton X-100 potentiated the activity of the enzyme from basophil leukemia cells and solubilized it, while it inhibited the activity of the leukotriene-synthesizing enzyme in the rat liver preparation. These results, along with a distinctly different inhibitor profile, indicate that LTC synthetase is a new and distinct glutathione S-transferase.
D000818:Animals; D001491:Basophils / Q000201:enzymology; D002460:Cell Line; D003600:Cytosol / Q000201:enzymology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D051381:Rats; D013189:SRS-A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D013189:SRS-A; D011464:Epoprostenol; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase; C035296:piriprost