Diiodotyrosine isolation

The coupling of two molecules of diiodotyrosine to give one molecule of thyroxine leads to the over-all loss of one alanine side chain, but the form in which this 3-carbon residue is removed is still not yet determined. Up till now, no work has been done on this reaction in the thyroid itself or in isolated thyroid tissues. All the evidence comes from in vitro incubations of diiodotyrosine or its derivatives modelled on von Mutzenbecher s experiments. Johnson and Tewkesbury (1942) found that after such incubations pyruvic acid and ammonia could be detected in the reaction mixture Ohno (see Roche and Michel, 1951) with the aid of chromatography was able to detect serine. Both of these compounds are likely results of the reaction, but at present neither of them has been confirmed. Experiments are still in progress (Pitt-Rivers, unpubhshed) to determine the nature of the alanine residue obtained during aerobic incuba tion of diiodotyrosine or its derivatives. It must, however, be emphasized that even if the nature of this residue were established in in vitro experiments, it would still be necessary to demonstrate that the same reaction takes place in the thyroid gland itself. 

Although earlier workers iodinated proteins, Ostwald in 1910 provided the first unequivocal proof that tyrosine in proteins was iodinated. He isolated diiodotyrosine from iodinated albumin (273), gliadin (274), and casein (275)-. Since then papers on serum albumin, egg albunun, and serum globulin (276), pepsin (6, 7), insulin (125), and the lactogenic hormone (277) all indicate that the action of iodine on these proteins in neutral or slightly alkaline solution is one of substitution on the tyrosine residues. The reaction is as follows ... 

Isolation. 3,5-Diiodotyrosine was first isolated by Drechsel (202) in 1896 from the alkaline hydrolysate of the homy skeleton of the coral Gorgonia cavolinii. This amino acid has been isolated from gorgonia skeletons (392, 393, 622, 769), bath sponges (41, 861), iodinated proteins (619-621), thyroid (374) and thyreoglobulin (320, 375). 

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