Peptide hormones iodination

Roth, J. (1975). Methods for assessing immunologic and biologic properties of iodinated peptide hormones. In Methods in Enzymology (B. W. O Malley and J. G. Hardman, eds.), Vol. 37B, pp. 223-233. Academic Press, New York. 

T4, T3, MIT, and DIT are stored outside the cell in the follicular colloid in peptide linkage within the Tg molecules. In normal humans on an iodine-sufficient diet, Tg makes up approximately 30% of the mass of the thyroid gland and represents a 2- to 3-month supply of hormone. The total amount of iodine contained as T4, T3, MIT, and DIT within Tg varies with the dietary iodine intake. 

Thyroglobulin. a glycoprotein, is composed of several peptide chains it also contains 0.5 to 1% iodine and 8 (o 10% carbohydrate in (he form of two types of poly.saccharide. The formation of thyroglobulin is regulated by TSH. Thyroglobulin has no hormonal properties. I( must be hydrolyzed to release the hormonal iodothyronines thyroxine and liothy-lonine (see Thyroid Hormones" in Chapter 19). 

The synthesis of T3, T4, DIT, and MIT in Tg molecules occurs mainly at the follicular ceU-colloid interface but also within the colloid. Tg is present m highest concentrations within the colloid, where it is stored. The follicular cells engulf colloid globules by endocytosis these globules then merge with lysosomes in the foUicular cell. Lysosomal proteases break the peptide bonds between iodinated residues and Tg, and T4, T3, DIT, and MIT are released into the cytoplasm of the follicular cell. T4 and T3 diffuse into the systemic circulation after their liberation from Tg. DIT and MIT are deiodinated by an intracellular microsomal iodoty-rosine dehalogenase. The freed iodide is then reused for thyroid hormone synthesis. 

Quite apart from the feasibility or otherwise of synthesizing peptides possessing thyrocalcitonin-like activity, the amino acid composition of the molecule is of interest in that the preparation of iodinated hormone of high specific activity is necessary if radioimmunoassay is to be attempted. 

The answer is b. (Murray, pp 307-346. Scriver, pp 4029-4076. Sack, pp 121-138. Wilson, pp 287-317.) Thyroxine is a derivative of tyrosine. It is formed by the iodination and joining of peptide-linked tyrosyl residues of thyroglobulin. Proteolysis of thyroglobulin yields thyroxine. Thyroxine is also called tetraiodothyronine, or T, because of the four iodine atoms of the thyroid hormone. 

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. 

B. Thyroid-Stimulating Hormone (TSH) In thyroid cells, this peptide increases iodine uptake... 

The thyroid secretes two types of hormones iodine-containing amino acids (thyroxine and triiodothyronine) and a peptide (calcitonin). Thyroxine and triiodothyronine have very general effects on growth, development, and metabolism. Calcitonin is important in calcium metabolism and is discussed in Chapter 41. This chapter describes the drugs used in the treatment of hypothyroidism and hyperthyroidism (Figure 38-1). 

There has been much speculation in the past on the nature of the circulating thyroid hormone whether it was a simple amino acid, a peptide or polypeptide of thyroxine, or thyroglobulin itself. In 1948 Taurog and Chaikoff produced a considerable amount of evidence that the plasma hormone was indeed thyroxine. Labeled plasma iodine behaved chemically in a manner identical with that of thyroxine added to plasma it was nondialyzable it was precipitated with plasma proteins with zinc hydroxide it was extractable with butanol, and it could be fractionated with carrier thyroxine by its partition between immiscible solvents. This work received confirmation from Laidlaw (1949), and it then became generally accepted that thyroxine alone was the circulating hormone. 

Due to the ease of handling and efficiency, the Chloramine-T method is still the most widely used radioiodination procedure and represents an effective way to label a variety of proteins and peptides such as albumins, globulins, neuropeptides, and chemokines. Several other methods, such as the enzymatically catalyzed iodination with lactoperoxidase, have been developed. These methods allow the labeling with mild reaction conditions. In the case of extreme oxidation, sensitive proteins such as pituitary hormones and reactive pre-iodinated compounds such as the Bolton and Hunter reagent can be used to incorporate radioiodine. 

There is reason to believe that the actual hormone is a compound of thyroxine, since preparations of gland protein have been obtained that are more effective than pure thyroxine, and act more rapidly. Also, thyroxine has been isolated from the thyroid as a peptide component. The residual iodine of the gland is present as the physiologically inert di-iodo-tyrosine. 

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