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MULTIPLE BINDING SITES OF HUMAN BRAIN AND LIVER MONOAMINE OXIDASE: SUBSTRATE SPECIFICITIES, SELECTIVE INHIBITIONS, AND ATTEMPTS TO SEPARATE ENZYME FORMS
Author(s) -
White Helen L.,
Glassman Ann T.
Publication year - 1977
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.1471-4159.1977.tb06502.x
Subject(s) - tryptamine , phenethylamine , monoamine oxidase , chemistry , tyramine , serotonin , biochemistry , monoamine oxidase b , monoamine oxidase a , substrate (aquarium) , inner mitochondrial membrane , enzyme , monoamine neurotransmitter , membrane , biological membrane , stereochemistry , biology , receptor , ecology
— MAO of human brain and liver mitochondria was solubilized by a procedure that preserved the substrate and inhibitor selectivities of the original mitochondrial preparation. Techniques that are designed to separate proteins on the basis of molecular size or net surface charge did not yield a physical separation of enzymically active A and B forms, even in the presence of ionic detergents or with limited proteolysis. However, sulfhydryl inhibitors, inorganic salts, ionic detergents, heat treatment, and sonication all tended to cause selective inactivation of serotonin‐metabolizing activity in solubilized preparations. Experiments with selectively inhibited (membrane‐bound or solubilized) MAO supported the concept of at least two independent kinds of substrate binding site, only one of which metabolizes serotonin (A type) and another (B type) which has a very strong affinity for β‐phenethylamine. l ‐Norepinephrine, tryptamine, dopamine, and tyramine could be classified as common substrates. The lowest K m values were found for tryptamine at A sites and for β‐phenethylamine at B sites. Results of this study suggest that the different MAO sites could be part of the same large molecular complex, which may normally be embedded in the outer mitochondrial membrane so that A sites are more dependent on their lipid environment within this membrane.