title: Does the aromatic L-amino acid decarboxylase contribute to thyronamine biosynthesis?
abstract: Thyronamines (TAM), recently described endogenous signaling molecules, exert metabolic and pharmacological actions partly opposing those of the thyromimetic hormone T(3). TAM biosynthesis from thyroid hormone (TH) precursors requires decarboxylation of the L-alanine side chain and several deiodination steps to convert e.g. L-thyroxine (T(4)) into the most potent 3-T(1)AM. Aromatic L-amino acid decarboxylase (AADC) was proposed to mediate TAM biosynthesis via decarboxylation of TH. This hypothesis was tested by incubating recombinant human AADC, which actively catalyzes dopamine production from DOPA, with several TH. Under all reaction conditions tested, AADC failed to catalyze TH decarboxylation, thus challenging the initial hypothesis. These in vitro observations are supported by detection of 3-T(1)AM in plasma of patients with AADC-deficiency at levels (46 ± 18 nM, n=4) similar to those of healthy controls. Therefore, we propose that the enzymatic decarboxylation needed to form TAM from TH is catalyzed by another unique, perhaps TH-specific, decarboxylase.
authors: Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Germany.
authors: Carolin S
authors: CS
authors: Hoefig
authors: Kostja
authors: K
authors: Renko
authors: Susanne
authors: S
authors: Piehl
authors: Thomas S
authors: TS
authors: Scanlan
authors: Mariarita
authors: M
authors: Bertoldi
authors: Thomas
authors: T
authors: Opladen
authors: Georg Friedrich
authors: GF
authors: Hoffmann
authors: Jeannette
authors: J
authors: Klein
authors: Oliver
authors: O
authors: Blankenstein
authors: Ulrich
authors: U
authors: Schweizer
authors: Josef
authors: J
authors: Köhrle
mesh_terms: D000409:Alanine / Q000378:metabolism; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002853:Chromatography, Liquid; D003653:Decarboxylation; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D015398:Signal Transduction; D012996:Solutions; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*; D013970:Thyronines / Q000096:biosynthesis
chemical_list: D012996:Solutions; D013963:Thyroid Hormones; D013970:Thyronines; D007980:Levodopa; C004547:thyronamine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D000409:Alanine; D004298:Dopamine