Iodination of tyrosine

Thiocyanate ion, SCN , inhibits formation of thyroid hormones by inhibiting the iodination of tyrosine residues in thyroglobufin by thyroid peroxidase. This ion is also responsible for the goitrogenic effect of cassava (manioc, tapioca). Cyanide, CN , is liberated by hydrolysis from the cyanogenic glucoside finamarin it contains, which in turn is biodetoxified to SCN. 

Additional kinetic evidence supporting molecular iodine as an iodinating species is sparse. Li325 found that the iodination of tyrosine in acetate buffers at 25 °C showed the mixed inverse dependence on iodide ion concentration noted above, so that part of the reaction appeared to involve the molecular species. Subsequently, Doak and Corwin326 found that the kinetics of the iodination of (N-Me)-4-carboethoxy-2,5-dimethyl- and (N-Me)-5-carboethoxy-2,4-dimethyl-pyrroles in phosphate buffers in aqueous dioxane at 26.5 °C obeyed equation (162), viz. 

Figure 12.2 The iodination of tyrosine or histidine residues in proteins by H2OI+.

Thioamides are reducing agents. They inhibit thyroid hormone synthesis by inhibiting the peroxidase enzymatic system, which catalyzes oxidation of iodide ions and iodine that are consumed in food, which is necessary for iodination of tyrosine derivatives. Thus they reduce the concentration of free iodine necessary to react with tyrosine derivatives, and they can also block oxidative addition reactions of mono- and diiodtyrosines, which form L-thyroxine and L-triiodothyronin. 

It inhibits oxidation of iodide, inhibits iodination of tyrosine residue and inhibits the coupling of iodotyrosine residue. After oral administration, it is rapidly absorbed and metabolised to methimazole which is active form and crosses the placental barrier. 

Fig. 18. Iodination of tyrosine (top) and histidine (bottom) amino acid residues in proteins by electrophilic substitution.

It is possible to alter amino-acid residues to see if this perturbs the EPR signal, e.g. by iodination of tyrosine residues [142]. Recently site-directed mutagenesis has been used extensively for this purpose. Whilst this can yield definitive negative results it is unlikely to lead to clear positive identification of a... 

The partial iodination of tyrosine in wool by propanolic iodine and its lack of reaction in butanol are explained by the observation that iV-acetyl-tyrosine ethyl ester is more extensively iodinated in ethanol than in propanol (Crewther and Dowling, unpublished observations, 1962). Solutions of I2 in n-butanol do not react with the tyrosine derivative. The results of iodination in different solvents are therefore attributable to differences in chemical equilibria. 

Thyroid hormone synthesis requires oxidation of dietary iodine, followed by iodination of tyrosine to mono- and diiodotyrosine coupling of iodotyrosines leads to formation of the active molecules, tetraiodo-tyrosine, (T or L-th3rroxine) and triiodotyrosine (Tj or L-thyronine). 

Radiolabelling is often performed by oxidation of iodide by different agents for iodination of tyrosine and histidine residues in peptides. However, unfavourable oxidation reactions can occur simultaneously, e.g., cysteine and methionine can be oxidized to their corresponding sulphone or sulphonic acid, so that neutral amino acids are converted to highly acidic groups, thus changing the electrostatic distribution within the structme of the... 

The method described by Morrison and Bayse (1970) for the enzymic iodination of tyrosine can be readily adapted to the modification of proteins. The reaction mixture contains, in order of addition, L-tyrosine (8.1x10 M), KI (1.0 xlO M), lactoperoxidase (7.4 X 10 M), in 0.05 M K-phosphate buffer, containing 1 x 10 M EDTA, at pH 7.4. The iodination is initiated by the addition of H2O2 to a concentration of 1.0 x 10 M. The specific activity observed for lactoperoxidase under these conditions was 1.05 x 10 moles of L-3-iodotyrosine per min per mole of enzyme at 25°C. At pH 7.4, the rate of enzymatic conversion of L-3-iodotyrosine to L-3,5-diiodotyrosine was 0.34 that of monosubstitution (Morrison and Bayse 1970). The desired level of iodination can be attained by successive equimolar additions of KI and HjOj to the reaction mixture. In this manner, only a low concentration of H2O2 is maintained, minimizing oxidation reactions. The concentration of lactoperoxidase may be calculated from the millimolar extinction coefficient of 114 at 412 run, while the concentrations of stock H2O2 solutions may be determined from the absorbance at 230 nm and a molar extinction coefficient of 72.4 (Phillips and Morrison 1970). 

Iodine, concentrated in the follicular cells by a pump in the cell membrane, is oxidized by a peroxidase. Iodination of tyrosine residues in thyroglobulin produces monoiodotyrosine (MIT) and diiodotyrosine (DIT), which undergo coupling reactions to produce 3,5,3-triiodothy-ronine (T3) and 3,5,3, 5 -tetraiodothyronine (T4). 

Jirousek, L., Pritchard, E. On the chemical iodination of tyrosine with protein sulfenyl iodide and sulfenyl periodide derivatives. Biochim. Biophys. Acta 1971, 243, 230-238. 

A number of important products are formed from tyrosine which, although quantitatively not of the same significance as those discussed above, are extremely important qualitatively. Among these are the hormone thyroxine, which is formed from the iodination of tyrosine in the peptide link, migration of one of the aromatic chains to form thyroxine, and triiodothyronine in the peptide link, which after hydrolysis in the thyroid gland, releases thyroxine and triiodothyronine. 

Oxidation and Iodination. The oxidation of iodide to its active form and the iodination of tyrosine are catalyzed by thyroid peroxidase, a heme-containing enzyme that utilizes hydrogen peroxide (HjOj) as the oxidant. The peroxidase is membrane-bound and concentrated at the apical surface of the thyroid cells. The reaction forms mono- and diiodotyrosyl residues in thyroglobulin just prior to its extracellular storage in the lumen of the thyroid follicle. is formed near its site of utilization and is stimulated by a rise in cytosolic Cd . ... 

Iodide concentrations higher than normal inhibit iodination of tyrosine, an effect that is useful in the treatment of thyroid disease. Inadequate iodine intake results in diffuse enlargement of the thyroid (goiter). 

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