Inhibition of mitochondrial phospholipase A2 by mono- and dilysocardiolipin.
Phospholipase A2 extracted from the acetone powder of previously frozen rat liver mitochondria is strongly inhibited compared to the activity manifest before acetone powder preparation. Activity is substantially recovered upon partial purification of the enzyme by gel filtration chromatography. Inhibitor activity elutes in the void volume from the column and is obtained in the chloroform layer when void volume fractions are subjected to a Folch extraction. Structural studies support the inhibitor being monolysocardiolipin. Under the assay conditions employed, 1 molecule of the inhibitor per 5000 substrate molecules or 40 nM on a nominal concentration basis is I50 for the mitochondrial enzyme. The agent is similarly effective against pancreatic and snake venom phospholipases A2. Monolysocardiolipin and dilysocardiolipin prepared enzymatically from bovine heart cardiolipin are less potent than the material arising from rat liver cardiolipin by factors of 10- and 30-fold, respectively, yet are still highly potent compared to the other known inhibitors of this enzyme. Differences in acyl group composition, in the degree of acyl group oxidation, or in structural isomerism between the sn-1 and sn-2 positions of the lyso compounds may account for the difference in potency between the materials derived from rat liver and bovine heart.
Hormel Institute, University of Minnesota, Austin 55912.
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D000818:Animals; D002308:Cardiolipins / Q000494:pharmacology / Q000502:physiology; D007700:Kinetics; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D054467:Phospholipases A2; D051381:Rats; D011919:Rats, Inbred Strains
D002308:Cardiolipins; D008246:Lysophospholipids; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2