Thyroxine (T4) release from thyroglobulin and its T4-containing peptide by thyroid thiol proteases.
Two thiol proteases, TP-1 and TP-2, were purified 500- and 400-fold, respectively, from hog thyroid lysosomal extracts and examined for their activities as releasers of T4 1) from hog thyroglobulin, 2) a fragment (mol wt, approximately 15,000) prepared therefrom, and 3) a T4-containing peptide (19 amino acid residues) derived from the fragment, by measuring the liberation of free T4 with reversed phase HPLC. TP-1 released 8%, 55%, and 95% of the bound T4 present in thyroglobulin, the fragment, and the peptide, respectively, after incubation for 8 h. TP-2, on the other hand, released only 2% of the bound T4 in thyroglobulin and liberated no T4 from the fragment and the peptide. The release of T4 from thyroglobulin by the action of TP-1 was increased approximately 2-fold by the addition of TP-2. This synergistic effect suggested that TP-1 can release T4 from thyroglobulin much more efficiently after the protein has been partially degraded by the action of TP-2, which has only a poor T4-releasing activity. It also suggested that the T4-releasing activity of TP-1 markedly increases as the size of protein substrate is decreased. The amino acid composition of the T4-containing peptide was identical with that previously isolated from bovine thyroglobulin, and this peptide sequence has been shown to be derived from the NH2-terminal portion of the thyroglobulin. This suggests that TP-1 can release T4 at least from the NH2-terminal region of thyroglobulin.
D000818:Animals; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D013552:Swine; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000201:enzymology*; D013974:Thyroxine / Q000378:metabolism*; D013975:Thyroxine-Binding Proteins / Q000378:metabolism*
D010446:Peptide Fragments; D011412:Propanolamines; D013975:Thyroxine-Binding Proteins; C044751:U 10029A; D013954:Thyroglobulin; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D013974:Thyroxine