Differences in A and B forms of monoamine oxidase revealed by limited proteolysis and peptide mapping

Abstract

Monoamine oxidase (MAO, EC 1.4.3.4) is a mitochondrial outer membrane enzyme which deaminates amine transmitters in the nervous system and biogenic amines throughout the body. At least two types of MAO activity have been identified which differ in their specificities for substrates and sensitivities to inhibitors^1–3. Type A preferentially deaminates 5-hydroxy-tryptamine and noradrenaline and is more sensitive to inhibition by clorgyline. Type B deaminates phenylethylamine and benzylamine and is more sensitive to inhibition by deprenyl. Tissues from several species express MAO A alone, MAO B alone, or both types of MAO. Furthermore, the two types of activity follow different developmental sequences in certain tissues. Models to explain the molecular and genetic regulation of this enzyme⁴ raise two questions: (1) are there different enzyme molecules associated with A and B types of activity, and (2) if there is only one enzyme molecule, how do differences in the microenvironment of this enzyme within the outer mitochondrial membrane produce two types of activity? Attempts to separate and purify the different types of activity have involved solubilisation and lipid extraction procedures that alter the kinetics of the enzyme and differentially affect the A and B types of activity^5–8. Immunological studies^9,10 have produced equivocal results. None of these observations has elucidated the molecular basis of the differences between the types of MAO activity. Here, we have used the technique of proteolytic digestion and peptide mapping to demonstrate that there are distinct enzyme molecules associated with the A and B types of MAO activity. This finding implies that the A and B forms of MAO may be coded for by separate gene loci and represent evolutionarily related proteins which have diverged in function.