Disease relevance of IODOTYROSINE

• Since adequate clinical and chemical control of hyperthyroidism with antithyroid drugs and iodine was attained in the 8 Group I subjects without a decrease in the % T4I or T3I below that of normal thyroids, it suggests that inhibition of iodotyrosine coupling is not required for this effect [1].

High impact information on IODOTYROSINE

• Spatial requirement for coupling of iodotyrosine residues to form thyroid hormones [2].
• Thyroglobulin (Tg) is the substrate for thyroid hormone biosynthesis, which requires tyrosine iodination and iodotyrosine coupling and occurs at the apical membrane of the thyrocytes [3].
• Thyroid hormonogenesis in thyroglobulin results in the conversion of an "acceptor" iodotyrosine to a hormone residue and a "donor" iodotyrosine to a dehydroalanine residue [4].
• In the isolated microsomes the glycosylation of the acceptor tripeptides was time-dependent and the tripeptide with an iodotyrosine residue in the X position was found to be a poor substrate [5].
• Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species [6].

Biological context of IODOTYROSINE

• This human cell system has been utilized to examine a series of iodothyronine and iodotyrosine analogues for structure-activity relationships [7].
• The human iodotyrosine dehalogenase 1 (DEHAL1) gene is composed of six exons [8].

Anatomical context of IODOTYROSINE

• Radiolabeled material in both types of endosomes is comprised of high molecular weight, insulin-sized, and low molecular weight components, with B chain-labeled small molecular weight material in two peaks, one corresponding to iodotyrosine and one to small peptides (Mr less than 1500) [9].
• This suggestion was strengthened by the finding that only the cytosol of the RBC, not its membranes, rapidly degraded Tyr-MIF-1 to free iodine and iodotyrosine [10].
• Iodotyrosine release showed a biphasic Arrhenius plot with an activation energy of 17 kcal/mol above but 27 kcal/mol below 20 degrees C. These results indicate that cell membrane polypeptides require a temperature-limiting event as well as passage through an ion-sensitive compartment prior to their complete degradation to constituent amino acids [11].
• At 37 degrees C, 125I-insulin bound to adipocytes was rapidly degraded into small fragments or iodotyrosine [12].
• Serotonin concentration was significantly reduced (P less than 0.025) in the median eminence but not in the hypothalamus after iodotyrosine administration [13].

Associations of IODOTYROSINE with other chemical compounds

• The enzyme responsible for iodide salvage in the thyroid, iodotyrosine deiodinase, was solubilized from porcine thyroid microsomes by limited proteolysis with trypsin [14].
• Furthermore, the observed phenoxyl radical-mediated oxidation of MN is consistent with its previously reported potent inhibition of the coupling of hormonogenic iodotyrosine residues in Tg in the reaction that forms thyroid hormones [15].
• Aliquots of tissue extracts (25-100 microliters) were reacted overnight with 5-dimethylaminonaphthalene-1-sulfonyl chloride and their iodotyrosine and iodothyronine content determined by HPLC utilizing fluorimetric detection [16].
• More than 50% of the radioactivity which accumulates in the media from dividing cells during the first 4 h after labeling was trichloroacetic acid-soluble, and was identified as iodotyrosine [11].
• Inhibition of iodide uptake and cAMP generation by iodotyrosine was negated characteristically by 3-nitro-L-tyrosine, an inhibitor of iodotyrosine deiodinase, or by methimazole, an inhibitor of thyroid peroxidase [17].

Gene context of IODOTYROSINE

• Coupling of iodotyrosine catalyzed by human thyroid peroxidase in vitro [18].
• Improved assay method for activity of thyroid peroxidase-catalysed coupling of iodotyrosine residues of thyroglobulin utilizing h.p.l.c. for analysis of iodothyronines [19].
• Ferredoxin and ferredoxin reductase activities in bovine thyroid. Possible relationship to iodotyrosine deiodinase [20].
• The 30 nmol dose of AVP had no effect on the transport of iodide or iodotyrosine out of the brain [21].
• Iodotyrosine deiodinase was active in HEK293 cells transfected by DEHAL1 cDNA, but not in CHO cells [22].

Analytical, diagnostic and therapeutic context of IODOTYROSINE

• A major disadvantage of (131)iodine (I)-labeled monoclonal antibodies (MAbs) for radioimmunotherapy has been the rapid diffusion of iodotyrosine from target cells after internalization and catabolism of the radioiodinated MAbs [23].
• Gel exclusion chromatography of tryptic peptides and microsequenator analysis of tryptic glycopeptides showed that iodotyrosine was present at each of the only readily accessible residues in intact hormone: alpha Tyr21, alpha Tyr92, and alpha Tyr93 [24].
• In an attempt to improve the separation of the T4-containing peptides in thyroglobulin tryptic digests from the much more abundant iodotyrosine-containing ones, which are present as contaminants, we have used a very simple and fast step prior to the HPLC fractionation as it is a self-packed ion-exchange column chromatography [25].
• Gastric peroxidase activity is specifically stimulated by adrenalectomy and is inhibited by glucocorticoids which also inhibit iodotyrosine formation in stomach [26].
• At steady state about half of the label dissociated from the cells as iodoinsulin and about half as iodotyrosine, as judged by gel filtration and paper chromatography in two solvent systems [27].

References