Inhibition of aromatic L-amino acid decarboxylase activity by human autoantibodies.
A full-length rat cDNA clone encoding aromatic L-amino acid decarboxylase (AADC) (E.C. 4.1.1.28) was used for in vitro transcription and translation. The enzyme had catalytic activity (0. 2 pmol serotonin/microl lysate per min), and was stimulated 2.5-fold by the addition of excess pyridoxal phosphate. On size exclusion chromatography, AADC eluted as a single activity peak with an apparent mol. wt of 93 kD. This activity peak was immunoprecipitated by sera from patients with autoimmune polyendocrine syndrome type I (APS I) containing autoantibodies against AADC. Serum and purified IgG from these patients inhibited the enzyme activity (non-competitively) by 10-80%, while sera from APS I patients without autoantibodies and controls did not. This finding confirms and extends previous observations that APS I patients have inhibitory antibodies against key enzymes involved in neurotransmitter biosynthesis.
Husebye
E S
ES
Division of Endocrinology, Institute of Medicine, University of Bergen, Bergen, Norway. Eystein.Husebye@med.uib.no
Boe
A S
AS
Rorsman
F
F
Kämpe
O
O
Aakvaag
A
A
Rygh
T
T
Flatmark
T
T
Haavik
J
J
D000293:Adolescent; D000328:Adult; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics; D001323:Autoantibodies / Q000378:metabolism*; D002384:Catalysis; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D007106:Immune Sera; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000201:enzymology* / Q000276:immunology*; D014176:Protein Biosynthesis; D011732:Pyridoxal Phosphate / Q000494:pharmacology; D051381:Rats; D014158:Transcription, Genetic
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001323:Autoantibodies; D007106:Immune Sera; D011732:Pyridoxal Phosphate; D001142:Aromatic-L-Amino-Acid Decarboxylases