Investigations of the mechanism of selective inhibition of type B mitochondrial monoamine oxidase by phosphatidylserine.
Liposomes of phosphatidylserine (PS) were found to inhibit strongly the B-form of membrane bound monoamine oxidase (MAO) isolated from rat and bovine liver, while having no effect on the rat liver A-form. Use of 14C-liposomes demonstrated high levels of PS association with the membrane, which could not be removed by extensive washing with high ionic strength buffers. The inhibition of MAO-B was not reversed on further perturbation of the membrane by chaotropic agents, sonication, or treatment with additional liposome preparations of phosphatidylcholine or phosphatidylinositol. Partial reversal of the inhibition was found when the PS-treated bovine liver membrane was solubilized with the detergent octyl glucoside. PS, however, had no effect on a solubilized preparation of bovine liver MAO. These results suggest a specific interaction between MAO and PS rather than an indirect effect of bulk changes in membrane properties, but an intact membrane was, nevertheless, required to mediate the inhibition. Comparison of the decreases in apparent levels of MAO-B in rat liver mitochondrial membranes that were calculated from changes in relative catalytic activities with A and B specific substrates or changes in sensitivity to A-form specific reversible and irreversible inhibitors, all showed good quantitative correlation. Lineweaver-Burk plots of the effect of PS incorporation into bovine liver mitochondrial membranes on MAO oxidation of phenylethylamine exhibited the expected pattern for a noncompetitive inhibitor acting on a ping-pong mechanism bireactant enzyme. On the basis of these results, a possible in vivo role for the acidic phospholipids in regulating apparent levels of MAO from one tissue to another and/or in response to environmental effects is proposed.
D000818:Animals; D002417:Cattle; D003902:Detergents; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000201:enzymology; D008081:Liposomes; D008930:Mitochondria, Liver / Q000201:enzymology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism / Q000494:pharmacology*; D010743:Phospholipids / Q000494:pharmacology; D011189:Potassium Chloride; D051381:Rats; D011919:Rats, Inbred Strains
D003902:Detergents; D008081:Liposomes; D008996:Monoamine Oxidase Inhibitors; D010718:Phosphatidylserines; D010743:Phospholipids; D011189:Potassium Chloride