[Molecular genetics of aromatic L-amino acid decarboxylase]

Abstract

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 recombinant human AADC in COS cells and proved that the expressed enzyme decarboxylated both L-5-hydroxytryptophan to serotonin and L-dopa to dopamine. We have 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 hapoloid genome. We have mapped the gene to chromosome band 7p12.1-p12.3 by fluorescence 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.