[Discovery of monoamine oxidase forms A and B]

During the 1960's, reports suggesting the existence of multiple forms of monoamine oxidase (MAO) appeared with increasing frequency. In July 1968, two reports appeared in the same issue of Biochemical Pharmacology that established the existence of MAO-A and MAO-B. This terminology was unanimously accepted at an international meeting on MAO in 1971. MAO-A preferentially deaminates serotonin (5HT) and is selectively inhibited by harmine and clorgyline, while MAO-B preferentially deaminates phenethylamine and benzylamine, and is selectively inhibited by (-)deprenyl as well as low concentrations of pargyline. It was later found that MAO-A and MAO-B are encoded by separate genes. The two genes have identical exon-intron organizations, but differ with respect to their promoters. In humans both genes are located very close together on the short arm of the X chromosome (Xp21-p11). In mice, the MAO-A gene is also located on the X chromosome, but the chromosomal locations of the MAO-A and -B genes for other species appear to be unknown at present. Some degree of polymorphism seem to exist in both genes. Both forms probably occur naturally as homodimers in the mitochondrial outer membrane, raising the possibility of 3 variants of both MAO-A and -B in human females that are heterozygous for alleles at each locus. Highly specific antibodies for MAO-A and -B, respectively, have been produced, and immunohistochemical studies show that the two forms are differentially expressed in different cell types. In rat and primate brain MAO-A is restricted to catecholamine neurons, while MAO-B is largely restricted to serotonin neurons and astrocytes. Congenital lack of MAO-A is associated with mental retardation, impulsive aggressive behavior and other behavioral/neurological disorders. These results support the conclusion that both MAO-A and -B play predominantly protective roles in the organism.