The role of phospholipid in the multiple functional forms of brain monoamine oxidase.
The nature of phospholipid requirement and lipid-protein interactions for the multiple functional forms of monoamine oxidase was investigated by rebinding the purified phospholipid to a lipid-depleted brain mitochondrial preparation. It was found that phosphatidylinositol uniquely stimulated the monoamine oxidase A activity to 80% over that in the original intact mitochondria. Other negatively charged phospholipids, although not as potent, could fully or partially reactivate the A or the B activity. Phosphatidylserine was relatively more effective in restoring the B activity. Phosphatidylcholine, a zwitterionic phospholipid, reconstituted 70% of the A activity but did not influence the B. More importantly, efficiency-gradient analyses indicated a distinct nature in the mechanism of lipid-protein interactions for the negatively charged and the zwitterionic phospholipids. The potency of the negatively charged phospholipid decreased sharply with increasing lipid molecules. No further stimulation could be detected when the lipid to protein ratio reached about 30 molecules of the negatively charged phospholipid for 100,000 daltons of membrane protein. The negatively charged phospholipid appeared to bind directly to the monoamine oxidase protein boundary with a high affinity. Phosphatidylcholine might reassociate as the membrane fluid bilayer, which in turn modulated the monoamine oxidase A activity.
D000818:Animals; D001921:Brain / Q000201:enzymology*; D007700:Kinetics; D008051:Lipid Bilayers; D008297:Male; D008560:Membrane Fluidity; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology*; D008970:Molecular Weight; D008995:Monoamine Oxidase / Q000378:metabolism*; D010741:Phospholipases A; D010743:Phospholipids / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D008051:Lipid Bilayers; D008565:Membrane Proteins; D010743:Phospholipids; D008995:Monoamine Oxidase; D010741:Phospholipases A