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Does the aromatic l-amino acid decarboxylase contribute to thyronamine biosynthesis?
MedLine Citation:
PMID:  22061622     Owner:  NLM     Status:  Publisher    
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±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.
Carolin S Hoefig; Kostja Renko; Susanne Piehl; Thomas S Scanlan; Mariarita Bertoldi; Thomas Opladen; Georg Friedrich Hoffmann; Jeannette Klein; Oliver Blankenstein; Ulrich Schweizer; Josef Köhrle
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-28
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  -     ISSN:  1872-8057     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ireland Ltd.
Institut für Experimentelle Endokrinologie, Charité - Universitätsmedizin Berlin, Germany.
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