Does the aromatic l-amino acid decarboxylase contribute to thyronamine biosynthesis?

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

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24 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)195-201
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume349
Issue number2
DOIs
StatePublished - Feb 26 2012

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Keywords

  • Decarboxylation
  • L-DOPA
  • L-DOPA decarboxylase
  • LC-MS/MS
  • Thyroid hormone metabolism
  • Thyronamines

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Hoefig, C. S., Renko, K., Piehl, S., Scanlan, T. S., Bertoldi, M., Opladen, T., Hoffmann, G. F., Klein, J., Blankenstein, O., Schweizer, U., & Köhrle, J. (2012). Does the aromatic l-amino acid decarboxylase contribute to thyronamine biosynthesis? Molecular and Cellular Endocrinology, 349(2), 195-201. https://doi.org/10.1016/j.mce.2011.10.024