title: Progress in monoamine oxidase (MAO) research in relation to genetic engineering.
abstract: Monoamine oxidase (MAO) is an enzyme that oxidizes various physiologically and pathologically important monoamine neurotransmitters and hormones such as dopamine, noradrenaline, adrenaline, and serotonin. Two types of MAO, i.e. type A (MAO-A) and type B (MAO-B), were first discovered pharmacologically. MAO-A is inhibited by clorgyline; and MAO-B, by deprenyl. cDNAs MAO-A and MAO-B were cloned and their structures determined. MAO-A and MAO-B are made of similar but different polypeptides and encoded by different nuclear genes located on the X chromosome (Xp11.23). MAO-A and MAO-B genes consist of 15 exons with identical intron-exon organization, suggesting that they were derived from a common ancestral gene. Both enzymes require a flavin cofactor, flavin adenine dinucleotide (FAD), which binds to the cysteine residue of a pentapeptide sequence (Ser-Gly-Gly-Cys-Tyr). Both enzymes exist on the outer membrane of mitochondria of various types of cells in various tissues including the brain. In humans, MAO-A is abundant in the brain and liver, whereas the liver, lungs and intestine are rich in MAO-B. MAO-A oxidizes noradrenaline and serotonin; and MAO-B, mainly beta-phenylethylamine. In the human brain, MAO-A exists in catecholaminergic neurons, but MAO-B is found in serotonergic neurons and glial cells. MAO-A knockout mice exhibit increased serotonin levels and aggressive behavior, whereas MAO-B knockout mice show little behavioral change. The gene knockout mice of MAO-A or MAO-B, together with the observation that some humans lack MAO-A, MAO-B, or both have contributed to our understanding of the function of MAO-A and MAO-B in health and disease. MAO-A and MAO-B may be closely related to various neuropsychiatric disorders such as depression and Parkinson's disease, and inhibitors of them are the subject of drug development for such diseases.
authors.affiliation: Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan. tnagatsu@fujita-hu.ac.jp
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods* / Q000639:trends; D006801:Humans; D001523:Mental Disorders / Q000201:enzymology / Q000235:genetics; D008995:Monoamine Oxidase / Q000096:biosynthesis* / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics
chemical_list: D008995:Monoamine Oxidase