Squires R F
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.
Vopr Med Khim. 1997 Nov-Dec;43(6):433-9.
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.
在20世纪60年代，关于存在多种形式单胺氧化酶（MAO）的报道日益频繁。1968年7月，同一期《生化药理学》上出现了两篇报道，证实了MAO - A和MAO - B的存在。1971年在一次关于MAO的国际会议上，这一术语被一致接受。MAO - A优先使血清素（5HT）脱氨基，并被 harmine 和氯吉兰选择性抑制，而MAO - B优先使苯乙胺和苄胺脱氨基，并被（-）司来吉兰以及低浓度的帕吉林选择性抑制。后来发现MAO - A和MAO - B由不同基因编码。这两个基因具有相同的外显子 - 内含子结构，但启动子不同。在人类中，这两个基因都位于X染色体短臂（Xp21 - p11）上非常靠近的位置。在小鼠中，MAO - A基因也位于X染色体上，但目前其他物种中MAO - A和 - B基因的染色体位置似乎尚不清楚。两个基因似乎都存在一定程度的多态性。两种形式可能都以同源二聚体的形式自然存在于线粒体外膜中，这增加了人类女性中MAO - A和 - B各有3种变体的可能性，这些女性在每个位点的等位基因都是杂合的。分别针对MAO - A和 - B产生了高度特异性抗体，免疫组织化学研究表明这两种形式在不同细胞类型中差异表达。在大鼠和灵长类动物大脑中，MAO - A局限于儿茶酚胺能神经元，而MAO - B主要局限于血清素能神经元和星形胶质细胞。先天性缺乏MAO - A与智力迟钝、冲动攻击行为及其他行为/神经疾病有关。这些结果支持了MAO - A和 - B在生物体中主要起保护作用的结论。
