Thyronamines (TAM), recently described endogenous signaling molecules, exert metabolic and pharmacological actions partly opposing those of the thyromimetic hormone T3. 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 (T4) into the most potent 3-T1AM. 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-T1AM 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.

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

BERTOLDI, Mariarita;
2012

Abstract

Thyronamines (TAM), recently described endogenous signaling molecules, exert metabolic and pharmacological actions partly opposing those of the thyromimetic hormone T3. 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 (T4) into the most potent 3-T1AM. 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-T1AM 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.
l-DOPA, Thyronamines, Thyroid hormone metabolism, LC–MS/MS, l-DOPA decarboxylase, Decarboxylation
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/392092
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 29
social impact