Selective effects of proteases and phospholipase A2 on monoamine oxidases A and B of human brain and liver.
Human brain and liver mitochondria contain membrane-bound monoamine oxidase of both A and B types. Monamine oxidase-A (MAO-A), either membrane-bound or in detergent-solubilized extracts from these tissues, was selectively inhibited during incubations with trypsin, chymotrypsin, thermolysin, or papain. MAO-A in solubilized, but not in membrane-bound, preparations was also very sensitive to the action of phospholipase A2, while MAO-B was unaffected. Membrane-bound MAO-A of rat brain mitochondria was more sensitive to phospholipases and less sensitive to proteases than was human brain enzyme, indicating that these agents may reveal species differences in MAO properties. Human brain and liver MAO-A, either solubilized or bound in mitochondrial membranes, apparently contains basic and aromatic peptide moieties that are available to proteases. Hydrolysis of these peptide bonds leads to rapid denaturation unless substrate molecules stabilize the active site. Phospholipase A2 may disrupt the phospholipid microenvironment of MAO-A, the integrity of which is essential for MAO-A activity, but not for MAO-B. No interconversion of the two activities was observed. After phospholipase A2 treatment, remaining MAO-A activity was recovered in low-molecular-weight regions of a gel filtration gradient, suggesting that MAO-A subunits were released. Although these experiments argue against the proposal that phospholipids may regulate the ratio of A/B activities of a single enzyme molecule, it is conceivable that endogenous phospholipases or proteases in mitochondrial membranes may influence MAO-A activity independently of MAO-B activity.
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology*; D002918:Chymotrypsin / Q000494:pharmacology; D010450:Endopeptidases / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology*; D008996:Monoamine Oxidase Inhibitors; D009928:Organ Specificity; D010206:Papain / Q000494:pharmacology; D010740:Phospholipases / Q000494:pharmacology*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D051381:Rats; D013820:Thermolysin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D010206:Papain; D013820:Thermolysin