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.
Download PDF:
Keywords: monoamine oxidase, discovery of A and B forms, physiological role, monoamine oxidase inhibitors, antidepressants, mechanisms of antidepressant action
Citation:
Squires Richard F. (1997) The discovery of monoamine oxidases A and B. Voprosy Meditsinskoi Khimii, 43(6), 433-439.
et al. The discovery of monoamine oxidases A and B // Voprosy Meditsinskoi Khimii. - 1997. - V. 43. -N 6. - P. 433-439.
et al., "The discovery of monoamine oxidases A and B." Voprosy Meditsinskoi Khimii 43.6 (1997): 433-439.
Squires, Richard, F. (1997). The discovery of monoamine oxidases A and B. Voprosy Meditsinskoi Khimii, 43(6), 433-439.
Ozelius, L, Hsu, Y-P.P., Bruns, G, Powell, J.F., Chen, S., Weyler, W., Utterback, M, Zucker, D., Haines, J., Trofatter, J.A., Conneally, P.M., Gusella, J.F. and Breakefield, X.O., Genomics, (1988) 3: 53-58. Scholar google search
Hsu, Y-P P., Weyler, W., Chen, S, Sims, K.B., Rmehart, W.B., Utterback, M.C., Powell, J.P. and Breakefield, X.O., J. Neurochem., (1988) 51: 1321-1324. Scholar google search
Chen, S. and Weyler, W., Biochem., Biophys. Res. Comm., (1988) 156: 445-450. Scholar google search
Chuang, H.Y.K., Patek, D.R. and Hellerman, L, J. Biol. Chem., (1974) 249: 2381-2384. Scholar google search
Minamiura, N. and Yasunobu, K.T. Arch. Biochem., Biophys. (1978) 189: 481-489. Scholar google search
Sims, К.В., de la Chapelle, A., Norio, R., Sankila, E-M., Hsu, Y-P.P., Rinehart, W.B., Corey, T.J., Ozelius, L, Powell. J.F, Bruns, G, Gusella, J.F, Murphy, D. L. and Breakefield, X.O., Neuron, (1989)2: 1069-1076. Scholar google search
Medvedev, A.E, Shvedov, V.I., Chulkova, T.M., Fedotova, O.A., Saederup, E and Squires, R.F., Neurochem. Res. (1996) 21: 1521-1526. Scholar google search
Squires, R.F, Saederup, E. and Lajtha, A., J. Neurochem. (1988) 51: 837-842. Scholar google search
McCauley, R. and Racker, E, Mol. Cell. Biochem. (1973) 1: 73-81. Scholar google search
Cawthon, R.M. and Breakefleld, X. O., Nature (1979) 281: 692-694. Scholar google search
Kochersperger, L.M., Parker, E.L., Siciliano, M, Darlington, G.J. and Denney, R.M., J. Neurosci. Res. (1986) 16: 601-616. Scholar google search
Cases, O., Seif, I, Grimsby, J., Gaspar, P., Chen, K, Ponrnin, S., Mbller, U., Aguet, M., Babinet, С Shih, J.C. andDe Maeyer, K, Science(1995) 268: 1763-1766. Scholar google search
Brunner, H.G., Nelen, M, Breakefield, X.O., Ropers, H.H. and van Oost, B.A., Science (1993) 262:578-580. Scholar google search
Bach, A. W.J., Lan, N.C., Johnson, D.L., Abell, С W., Bembenek, M.E., Kwan, S-W., Seeburg, PH. and Shih, J.C., Proc. Natl. Acad. Sci. USA (1988) 85: 4934-4938. Scholar google search
Kearney, E.B., Salach, J.I., Walker, W.H., Seng, R.L., Kenney, W., Zeszotek, E. and Singer, T.P., Eur. J. Biochem. (1971) 24: 321-327. Scholar google search
Hsu, Y-P.P., Powell, J.F., Sims, КВ., Breakefield, X.O., J. Neurochem. (1989) 53:12-18. Scholar google search
Shih, J.C, Grimsby, J, Chen, K. and Zhn, O-s., J. Psychiatr. Neurosci. (1993) 18:25-32. Scholar google search
Levitt, P., Pintar, J.E. and Breakefield, X.O., Proc. Natl. Acad. Sci., USA (1982) 79: 6385-6389. Scholar google search
Westlund, K.N., Denney, R.M., Kochersperger, L.M., Rose, R.M. and Abell, C.W. Science (1985)230:181-183. Scholar google search
