Tetraiodothyronine thyroxine

The amino acid tyrosine is the starting point in the synthesis of the catecholamines and of the thyroid hormones tetraiodothyronine (thyroxine T4) and triiodothyronine (T3) (Figure 42-2). T3 and T4 are unique in that they require the addition of iodine (as T) for bioactivity. Because dietary iodine is very scarce in many parts of the world, an intricate mechanism for accumulating and retaining T has evolved. 

Antagonists of riboflavin include isoriboflavin, lumiflavin, aiaboflavin, hydroxyethyl analogue, formyl methyl analogue, galactoflavin, and flavin-monosulfate. Synergists include vitamins A. B, B(l, and B12, niacin, pantothenic acid, folic acid, biotin, tetraiodothyronine (thyroxine), insulin, and somatotrophin (growth hormone). 

Abbreviations BAT, brown adipose tissue BrAc, /V-bromoacetyl- BSA, bovine serum albumin CNS, central nervous system DEP, diethylpyrocarbonatc DIT, diiodotyrosine DTT, dithiothreitol G, glu-curonide Grx, glutaredoxin GSH, reduced glutathione GSSG, oxidized glutathione IRD. inner ring deiodination MIT, monoiodotyrosine ORD, outer ring deiodination PTU, propylthiouracil S, sulfate rT3, 3,3, 5 -triiodothyronine (reverse T,) Trx, thioredoxin T2, diiodothyronine T3, 3,3, 5-triiodothyronine T4, 3,3, 5,5 -tetraiodothyronine (thyroxine). 

Iodine is a powerful oxidizing agent and has a direct action on cells by precipitating proteins. The affected cells may be destroyed. In addition to the primary irritant action of iodine, this compound can act as a potent sensitizer. Iodine is an integral part of thyroid hormones (tetraiodothyronine (thyroxine) and triiodothyronine), and deficiency results in compensatory hyperplasia and hypertrophy of the thyroid gland (endemic goiter). Endemic goiter occurs naturally where soil is deficient in iodine. 

Using bis (trimethylsilyl) acetamide (BSA), volatile trimethylsilyl (TMS) derivatives of the active components 3,5,3, 5 -tetraiodothyronine (thyroxin, TJ and 3,5,3 -triiodothyronine (T3) have been prepared as well as TMS derivatives of the nonphysiologically active components 3,3, 5 -triiodothyronine (T3 ), 3,5-diiodothyronine (T2), and 3,5-diiodo-tyrosine (DIT). Separation and quantitative estimation of these iodinated amino acids is achieved by gas-liquid chromatography. The method is... 

Two iodine derivatives of tyrosine, triiodothyronine and tetraiodothyronine (thyroxine), act as important hormones in the body and are also amino acid components of the protein thyroglobulin (see p. 127). 

The preparation of iodothyronines labeled in different positions is necessary for metabolic studies which are required for the interpretation of the peripheral action of the thyroid hormone. 3,5-Diiodo-L-thyronine has been synthesized (34) from 3,5-diamino-p-methoxyphenosy-J r-acetyl-L-phenylalanine ethyl ester (diazotization, decomposition of the diazotization product by -f I, and hydrolysis of the 3,5-diiodo-p-methoxyphenoxy-iV>acetyl-L-phenylalanine ethyl ester) and labeled in the 3 and 5 positions. 3, 5 -DITh is necessary for the preparation of some of the labeled tri-and tetraiodothyronine (thyroxine). 

Thyroid Hormones. Iodine, absorbed as P, is oxidized in the thyroid and bound to a thyroglobulin. The resultant glycoprotein, mol wt 670,000, contains 120 tyrosine residues of which ca two-thirds are available for binding iodine in several ways. Proteolysis introduces the active hormones 3,5,3 -triiodothyronine (T ) and 3,5,3, 5 -tetraiodothyronine (T, (thyroxine) in the ratio Ty.T of 4 1 (121,122). 

Iodide ions and organic iodine compounds e.g. thyroxine, triiodo- and tetraiodothyronine... 

Derived from the amino acid tyrosine, thyroid hormones are unique because they contain iodine. At this time, its incorporation into thyroid hormones is the only known use for iodine in the body. There are two thyroid hormones, named for the number of iodides added to the tyrosine residues of the thyroglobulin triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine). Although significantly more T4 is synthesized by the thyroid gland, T3 is the active hormone. At the target tissue, T4 is deiodoninated to form the more potent T3. 

The normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42. 

Eukaryote organisms primarily respond to external signals by an initial signal perception by receptors. In general, such receptors can be either cytosolic or located on the plasma membrane [13-15]. The former mechanism applies to thyroid hormones (triiodothyronine and tetraiodothyronine or thyroxine), retinoids (e.g. retinoic acid), the insect developmental hormones such as ecdysone, steroid hormones (such as... 

Abbreviations 3,5,3, 5 -tetraiodothyronine or thyroxine, T4 3,5,3-triiodothyronine, T, 3,3, 5 -triio-dothyronine, reverse T, or r-T3 3,5,3, 5 -tetraiodothyroacetic acid, TETRAC 3,5,3 -triiodothyroacetic acid, TRIAC 3,5-diiodotyrosine, DIT 3-monoiodotyrosine, MIT thyrotropic hormone, TSH thyreo-liberin, TRH growth hormone, GH microtubule associated proteins, MAPs TAU protein, one of the brain MAPs. 

Fig. 1. Major thyroid hormones (3,5,3 ,5 -tetraiodothyronine or thyroxine, T4) and (3,5,3 triiodothy-ronine, T,) and other important iodothyronines (3,3,5 -triiodothyronine or reverse-T, r-T and 3,3 -diiodothyronine 3,3 -T2). T4 and T, are active, r-Tj and 3,3 -T, are inactive. The acetic derivatives of T4 (TETRAC) and T, (TRIAC) are produced by oxidative decarboxylation of the alanine side-chain and have thyromimetic activities.

Purines and pyrimidines are derived largely from amino acids. The biosynthesis of these precursors of DNA, RNA, and numerous coenzymes will be discussed in detail in Chapter 25. The reactive terminus of sphingosine, an intermediate in the synthesis of sphingolipids, comes from serine. Histamine, a potent vasodilator, is derived from histidine by decarboxylation. Tyrosine is a precursor of the hormones thyroxine (tetraiodothyronine) and epinephrine and of melanin, a complex polymeric pigment. The neurotransmitter serotonin (5-hydroxytryptamine) and the nicotinamide ring of NAD + are synthesized from tryptophan. Let us now consider in more detail three particularly important biochemicals derived from amino acids. 

The thyroid gland secretes two hormones, thyroxine (3,5,3, 5 -L tetraiodothyronine) and triiodothyronine (3,5>3 -L-triiodothyronine), which are commonly known as T4 and T3, respectively (Table 52-1). In addition, the thyroid gland secretes small amounts of biologically inactive 3,3, 5 -L-triiodothyronine (reverse T3 [rTa]) and minute quantities of monoiodotyrosine (MIT) and diiodotyrosine (DIT), which are precursors of T3 and T4. The structures of these compounds are shown in Figure 52-1. 

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. 

---