INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Inhibition of Thyroid Peroxidase by Nitric Oxide
Autor/es:
SCHÖPFER F; BOCANERA L; GROSSONI V; KRAWIEC L; CARRERAS MC; PODEROSO JJ
Lugar:
San Francisco, EEUU
Reunión:
Congreso; First International Conference Biology, Chemistry ad Therapeutic Applications of Nitric Oxide; 2000
Institución organizadora:
NO Society
Resumen:
Thyroid peroxidase (TPO) catalyzes the two steps of thyroxine biosynthesis: a) the iodination of thyrosil residues on thyroglobulin and b) the condensation of the iodotyrosyl residues into iodothyronines. Previous studies suggested that nitric oxide (NO) inhibits organification. The aim of this work was to demonstrate that NO specifically inhibits TPO. To that purpose, TPO was extracted from bovine thyroid membranes with 0.1% Triton and enzyme activity was measured as incorporation of  125I to thyroxine. After the exposure to 10-50 µM NO the TPO activity showed a maximal inhibition of 58 %. This effect was completely reverted by exposing the samples to room air for 7 min. Moreover, NO effects on TPO spectra were different from those induced by H2O2. This changes occurs in reduced TPO as well as in TPO exposed to H2O2. NO bound to native ferric TPO Fe (III) and resulted in TPO Fe (III)-NO formation. The association rate constant of NO with TPO was very high and characterized by the shift in absorbance peaks from 411 to 401 nm. Initial spectral changes were followed by a decay of nitrosyl intermediate species to an stable state associated to the recovery of enzyme