ヒト芳香族L-アミノ酸脱炭酸酵素の分子生物学的研究

概要

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Aromatic _L-amino acid decarboxylase (AADC) decarboxylates both _L-5-hydroxytryptophan to serotonin in serotonergic neurons and pineal cells, and _L-DOPA to dopamine in catecholaminergic neurons and adrenal medullary cells. Thus AADC produces two major mammalian neurotransmitters and hormones. We isolated and sequenced a full-length, neuronal-type, cDNA encoding human AADC. It consisted of 1932 bases containing an open reading frame encoding 480 amino acids residues with a molecular weight of 53,891. We expressed a recobinant human AADC in COS cells and proved that the expressed enzyme decarboxylated both _L-5-hydroxytryptophan to serotonin and _L-DOPA to dopamine. We cloned genomic DNA of human AADC and determined the structure. The genomic DNA of human AADC consists of 15 exons spanning about 100 kilobases and exists as a single copy in the haploid genome. We have mapped the gene to chromosome band 7p12.1-p12.3 by fluorescene in situ hybridization. We cloned the nonneuronal type cDNA from human liver and identified another first exon different from the neuronal type cDNA. This showed that an alternative usage of the first exon produced two types of mRNAs in AADC and suggested that alternative splicing would regulate the tissue-specific expression of AADC.
1994-02-25