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 variation in the clinical presentation of the disease. Sera from patients with autoimmune polyendocrine syndrome type I contain autoantibodies against the beta-cell proteins glutamate decarboxylase and an unrelated 51-kDa antigen. By screening of an expression library derived from rat insulinoma cells, we have identified the 51-kDa protein as aromatic-L-amino-acid decarboxylase (EC 4.1.1.28). In addition to the previously published full-length cDNA, forms coding for a truncated and an alternatively spliced version were identified. Aromatic L-amino acid decarboxylase catalyzes the decarboxylation of L-5-hydroxytryptophan to serotonin and that of L-3,4-dihydroxyphenylalanine to dopamine. Interestingly, pyridoxal phosphate is the cofactor of both aromatic L-amino acid decarboxylase and glutamate decarboxylase. The biological significance of the neurotransmitters produced by the two enzymes in the beta cells remains largely unknown.
Rorsman
F
F
Department of Internal Medicine, University Hospital, Uppsala University, Sweden.
Husebye
E S
ES
Winqvist
O
O
Björk
E
E
Karlsson
F A
FA
Kämpe
O
O
D000293:Adolescent; D000311:Adrenal Glands / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D015723:Gene Library; D006066:Gonads / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008969:Molecular Sequence Data; D010280:Parathyroid Glands / Q000276:immunology; D016884:Polyendocrinopathies, Autoimmune / Q000145:classification / Q000276:immunology*; D011233:Precipitin Tests; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000276:immunology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013577:Syndrome
D001324:Autoantigens; D011994:Recombinant Proteins; D001142:Aromatic-L-Amino-Acid Decarboxylases