Thyroid peroxidase in dyshormonogenetic goiters with organification and thyroglobulin defects.
Thyroid peroxidase (TPO) iodide and guaiacol oxidation activities were evaluated in eight dyshormonogenetic goiters. Two of these had a defective thyroglobulin; the TPO iodide oxidation (431 and 316 U/g ptn) and iodination (31 and 8.6 nmol I/mg ptn) activities were within the normal ranges. The goiters from two siblings with positive perchlorate iodide discharge tests also had normal TPO iodide oxidation (602 and 299 U/g ptn) and iodination activities (44 and 11 nmol I/mg ptn). No TPO iodide oxidation activity was found in the goiters from the other four patients with positive perchlorate iodide discharge tests, and TPO iodide oxidation inhibitory activities were detected in both their TPO and thyroglobulin preparations. Three of them had some TPO guaiacol oxidation activity and did not inhibit normal guaiacol oxidation. The TPO preparation immunoblot of these three goiters showed a faintly visible band of normal 100 kDa TPO. However, in the other patient no guaiacol oxidation activity was detected, and only two bands of low-molecular-weight TPO (72 and 43 kDa) were found, again showing that iodine organification defects in dyshormonogenetic goiters can be due to either qualitative or quantitative TPO defects. The TPO inhibition diminished when iodide was increased in the assay, but was not altered by increasing cofactor (H2O2). Our results, so far, suggest that the TPO-inhibitory substance may interact reversibly with a specific iodide site on the enzyme or with the oxidized form of iodide, and/or could bind free iodide, making it unavailable for enzymatic oxidation.
de Carvalho
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Instituto de Biofísica Carlos Chagas Filho, Univerisdade Federal do Rio de Janeiro, Brasil.
Rego
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Rosenthal
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D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D006042:Goiter / Q000201:enzymology* / Q000473:pathology; D006139:Guaiacol / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism*; D007454:Iodides / Q000378:metabolism*; D013954:Thyroglobulin / Q000378:metabolism*
D007454:Iodides; D006139:Guaiacol; D013954:Thyroglobulin; D007453:Iodide Peroxidase