Iodinated tyrosine

Figure 12.6 The immobilized glucose oxidase/lactoperoxidase system radioiodinates proteins through the intermediate formation of hydrogen peroxide from the oxidation of glucose. H2O2 then reacts with iodide anions to form reactive iodine (I2). This efficiently drives the formation of the highly reactive H2OI+ species that is capable of iodinating tyrosine or histidine residues (see Figure 12.2).

The iodinated tyrosine residues monoiodotyrosine (MIT) and diiodoty-rosine (DIT) combine (couple) to form iodothyronines in reactions catalyzed by thyroid peroxidase. Thus, two molecules of DIT combine to form T4, and MIT and DIT join to form T3. 

Others This includes iodine that can be used to mono- or di-iodinate tyrosine residues. 

The following sparingly soluble chloroamide together with I will also iodinate tyrosine and can be used to incorporate radiolabeled iodine into proteins.285,286... 

Thyroid cells actively transport iodine (I-), which is incorporated into a few tyrosine residues of thyroglobulin by the enzyme iodoperoxidase. After condensation of iodinated tyrosine residues, the thyroglobulin is proteolytically degraded liberating thyroxine and triiodothyronine. 

Figure 265 IODO-BEADS contains immobilized Chloramine-T functional groups that can react with radioactive iodide in aqueous solution to form a highly reactive intermediate. The active species may be an iodosulfonamide derivative, which then can iodinate tyrosine or histidine residues in proteins.

Marine tunicates are also a source of brominated tyrosine derivatives. The colonial ascidian Aplidium sp., which was collected in Australia, yielded the novel iodinated tyrosine alkaloids 1973-1975 (1819). Collections of Botryllus sp. and Botryllus schlosseri from the Philippines and the Great Barrier Reef, respectively, have afforded botryllamides A-D (1976-1979) (1820). A Palauan ascidian Botrylloides tyreum produces several new botryllamides, including the brominated botryllamide G (1980) (1821). The simple brominated tyramines 1981 and 1982 were isolated from the New Zealand ascidian Cnemidocarpa bicornuta (1822) and an Indonesian Eudistoma sp. ascidian (1823). 

The chemical structures of thyroxine and triiodothyronine are shown in Figure 31—1. As shown in the figure, thyroid hormones are synthesized first by adding iodine to residues of the amino acid tyrosine. Addition of one iodine atom creates monoiodotyrosine, and the addition of a second iodine creates diiodotyrosine. Two of these iodinated tyrosines are then combined to complete the thyroid hormone. The combination of a monoiodotyrosine and a diiodotyrosine yields triiodothyronine, and the combination of two diiodoty-rosines yields thyroxine.55... 

The third step in thyroid hormone synthesis is cleavage of the aromatic R group from one of the iodinated tyrosines in the dimer. As a result, one of the iodotyros-... 

The second step in thyroid hormone synthesis is the covalent bridging of two different residues of iodinated tyrosine. A dimer is formed, reminiscent of the dimers of cysteine in proteins (the cysteine dimer is called cystine). Only a small fraction of the iodinated tyrosines is bridged in this way. More specifically, only four of the iodinated tyrosines, located at positions 5,2555,2569, and 2748, participate in the reaction. The numbers refer to the amino acid, cormting from the amino terminus of the protein. Thyroglobulin has 2748 amino acids. The first and second steps are catalyzed by thyroperoxidase, a heme protein. It requires hydrogen peroxide for activity. To summarize, thyroperoxidase catalyzes the attachment of iodine atoms to residues of tyrosine as well as the subsequent cross-linking of the iodinated tyrosine residues. 

Many derivatives of histidine are not stable to acid hydrolysis and are not discussed here (however, see 2.12.2 for those that occur naturally in proteins). Brief mention should be made of the iodination of histidyl residues by HOI ( 3.7.2). The mono- and diiodohistidines can be identified and distinguished from the iodinated tyrosines by high voltage paper electrophoresis in 1 M formic acid (Roholt and Pressman 1972) after complete enzymic hydrolysis of the protein or peptide ( 2.11 Roholt and Pressman 1972). Quantitation and identification are facilitated by the use of radiolabeled reagent. 

Figure 11-11 depicts the several structures relevant to this discussion. The thyroid hormones and precursors are all iodinated tyrosine derivatives, and their iodine content is undoubtedly a unique occurrence in mammals. 

The mechanism of thyroglobufin (Tg) iodination has been intensely debated and remains an open question the specific controversy focuses on whether or not iodination of Tg tyrosyl groups occurs via an enzyme-bound intermediate, or by freely diffusing iodination equivalents released from TPO. It is clear, however, that TPO actuates nonspecific iodination reactions in the thyroid. The two chemical species of iodine that can iodinate biomolecules under physiologic conditions are HOI and I2. Dunford and Ralston (1983) demonstrated that HOI, not I2, is the primary species that iodinates tyrosine in aqueous environments that contain both I2 and HOI. I2 is likely to be the species that is responsible for the iodination of lipids. The distinct pharmacological and toxicological properties of iodide and oxidized iodide (I2) have been a topic of some interest in the literature, as some activity not associated with THs has been ascribed to I2. 

It was further found by these authors that the dehalogenase was inactive towards the iodinated tyrosines when they were bound in thyroglobulin only free amino acids were attacked (personal communication). The metabolism of the iodinated tyrosines can therefore be regarded as taking place entirely within the thyroid after proteolysis from thyroglobulin they are completely dehalogenated and the iodide formed can be re-utilized for the cycle of thyroid hormone synthesis. 

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