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Selective Effects of Proteases and Phospholipase A 2 on Monoamine Oxidases A and B of Human Brain and Liver
Author(s) -
White Helen L.,
Stine Deborah K.
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb12766.x
Subject(s) - proteases , monoamine neurotransmitter , phospholipase , monoamine oxidase , chemistry , biochemistry , human brain , neuroscience , biology , enzyme , serotonin , receptor
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 A 2 , 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 activesite. Phospholipase A 2 may disrupt the phospholipid microenvironment of MAO‐A, the integrity of which is essential for MAO‐A activity, but not for MAO‐B. No in‐ terconversion of the two activities was observed. After phospholipase A 2 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.