AROMATIC-L-AMINO-ACID DECARBOXYLASE, A PYRIDOXAL PHOSPHATE-DEPENDENT ENZYME, IS A BETA-CELL AUTOANTIGEN

Different autoantigens are thought to be involved in the pathogenesis of insulin-dependent diabetes mellitus, and they may account for the v ariation in the clinical presentation of the disease, Sera from patien ts with autoimmune polyendocrine syndrome type I contain autoantibodie s against the beta-cell proteins glutamate decarboxylase and an unrela ted 51-kDa antigen, By screening of an expression library derived from rat insulinoma cells, we have identified the 51-kDa protein as aromat ic-L-amino-acid decarboxylase (EC 4.1.1.28). In addition to the previo usly published full-length cDNA, forms coding for a truncated and an a lternatively spliced version were identified, Aromatic L-amino acid de carboxylase catalyzes the decarboxylation of L-5-hydroxytryptophan to serotonin and that of L-3,4-dihydroxyphenylalanine to dopamine, Intere stingly, pyridoxal phosphate is the cofactor of both aromatic L-amino acid decarboxylase and glutamate decarboxylase. The biological signifi cance of the neurotransmitters produced by the two enzymes in the beta cells remains largely unknown.