TY - JOUR
T1 - Does the aromatic l-amino acid decarboxylase contribute to thyronamine biosynthesis?
AU - Hoefig, Carolin S.
AU - Renko, Kostja
AU - Piehl, Susanne
AU - Scanlan, Thomas S.
AU - Bertoldi, Mariarita
AU - Opladen, Thomas
AU - Hoffmann, Georg Friedrich
AU - Klein, Jeannette
AU - Blankenstein, Oliver
AU - Schweizer, Ulrich
AU - Köhrle, Josef
N1 - Funding Information:
This work is supported by grants from the Deutsche Forschungsgemeinschaft (DFG Graduiertenkolleg 1208, TP3 J.K. & U.S.) and the Charité-Universitätsmedizin Berlin to J.K.
PY - 2012/2/26
Y1 - 2012/2/26
N2 - 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 1AM. 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 1AM in plasma of patients with AADC-deficiency at levels (46±18nM, 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.
AB - 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 1AM. 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 1AM in plasma of patients with AADC-deficiency at levels (46±18nM, 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.
KW - Decarboxylation
KW - L-DOPA
KW - L-DOPA decarboxylase
KW - LC-MS/MS
KW - Thyroid hormone metabolism
KW - Thyronamines
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U2 - 10.1016/j.mce.2011.10.024
DO - 10.1016/j.mce.2011.10.024
M3 - Article
C2 - 22061622
AN - SCOPUS:84862608054
SN - 0303-7207
VL - 349
SP - 195
EP - 201
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 2
ER -