Triiodothyronine, biosynthesis

There are three plausible pathways for the biosynthesis of triiodothyronine. It could be formed from one molecule each of mono- and diiodotyrosine in the same way as thyroxine can be formed from two molecules of diiodotyrosine or it could be formed by incomplete iodination of preformed thryonine or diiodothyronine or it could be formed by deiodina-tion of thyroxine. Formation by deiodination is favored by English work-... 

Figure 45-2. Biosynthesis of the thyroid hormones Tj and in the thyroid follicular cell and release into the bloodstream. Abbreviations are as follows TG, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyrosine Tj, triiodothyronine T., thyroxine.

The biosynthesis of thyroid hormone proceeds with the coupling of an MIT and a DIT residue to form a triiodothyronine (T3) residue or of two DIT residues to form a tetraiodothyronine (T4) residue. T3 and T4 are stored in the thyroid follicle as amino acid residues in thyroglobulin. Under most circumstances, the T4/T3 ratio in thyroglobulin is approximately 13 1. 

Fig. 1. Schematic representation of the pathways of the biosynthesis of the thyroid hormones. The sites of biosynthetic defects are also indicated. [L] = active iodide," MIT = monoiodotyrosine, DIT = diiodotyrosine, Ts — triiodothyronine, T = thyroxine, TBP = thyroid hormone-binding proteins.

The relevance of the results obtained in vitro, in either liver slices or perfusates, to the general problem of lipoprotein biosynthesis in the intact animal remains to be established. In vivo synthesis of the protein moiety of serum 3-lipoprotein was studied in roosters by administration of S -methionine (Florsheim et al., 1963), followed by measurements of specific radioactivity of plasma 3-lipoprotein separated by dextran sulfate. Under these experimental conditions, enhancement of methionine incorporation was noted after pharmacological doses of ethanol, estrogens, and triiodothyronine. No significant effect was obtained after administration of epinephrine, cortisone, and thyroxine preparations. 

With regard to the biosynthesis of triiodothyronine, two pathways are possible (1) enzymic reduction of one iodine atom from thyroxine, and (2) the coupling of one molecule of monoiodotyrosine with one molecule of diiodotyrosine. These alternative pathways are shown in the following diagram ... 

The biosynthesis of flavocoenzymes is regulated by the supply of riboflavin, competition for ATP and hormonal balances. Increasing riboflavin concentrations in the intestinal lumen decreases the rate of vitamin absorption, while riboflavin deficiency leads to increased absorption efiiciency. The hormones thyroxine and triiodothyronine stimulate FMN and FAD synthesis in mammals by increasing the activity of flavokinase and for this reason hypothyroidism leads to reduced tissue levels of flavins. In the kidney, aldosterone promotes an increase in the activity of fla vokinase and therefore an increase of flavins. 

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