Thyroid hormone chemistry

Figure 16.9 Metabolism of iodine and the formation of thyroid hormones. Note that the thyroid gland produces one type of triiodothyronine, whereas peripheral tissue dehalo-genases produce another type. (Adapted by permission from Chattoraj SC, Watts NB. Endocrinology. In Tietz NW, ed. Textbook of Clinical Chemistry. Philadelphia WB Saunders, 1986, p. 1117.)...

Only a minority (25 to 30) of clinical chemistry analytes are traceable to SI units (e.g., electrolytes), some metabolites (glucose, creatinine, and uric acid), steroid, and some thyroid hormones. With protein hormones, the existence of heterogeneity or microheterogeneity complicates the problem of traceability. 

Figure 52-3 Formation and secretion of thyroid hormone. Iodine transport into the gland is inhibited by anions such as thiocyanate (SCN ), perchlorate (C 0 ), and pertechnetate (TcO ). The oxidation and organic binding of iodide to thyroglobuiin are blocked by thioureas, sulfonamides, and high concentrations of iodide. (Modified from Berger S, Quinn JLThyroid function. ln Tietz NW, ed. Fundamentals of clinical chemistry, 2nd ed. Philadelphia WB Saunders Co, 1976 585.)...

FeMoCo in nitrogenase Anti-cancer Ru drugs Pd-catalysts 2010 Chemistry Nobel Prize- Ubiquitous toxic environmental pollutant Alloyed with Cu in bronze and with Pb in pewter Thyroid hormones, T3, T4 ... 

Baxter, J.D., Fletterick, R.J., Webb, P. and Guy, R.K. (2005) Discovery of small molecule inhibitors of the interaction of the thyroid hormone receptor with transcriptional coregulators. The Journal of Biological Chemistry, 280, 43048 -3055. 

Cunha Lima, S.T., Webb, P., Baxter, J.D. and Scanlan, T.S. (2002) Rational design and synthesis of a novel thyroid hormone antagonist that blocks coactivator recruitment. Journal of Medicinal Chemistry, 45, 3310—3320. 

Yoshihara, H.A., Baxter, J.D., Ribeiro, R.C. and Scanlan, T.S. (1998) A high-affinity subtype-selective agonist ligand for the thyroid hormone receptor. Chemistry el Biology, 5, 299-306. 

Maglich, J.M., Watson, J., McMillen, P.J., Goodwin, B., Willson, T.M. and Moore, J.T. (2004) The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. The Journal of Biological Chemistry, 279, 19832-19838. 

The concept of cis-trans (Z-E) isomerism, originally used for the description of the relative geometry of olefins, has been extended to many other functions which feature a double bond character (pseudo double bonds), such as amides, as well as single bonds with a partial or complete limited rotation due to steric or stereoelec-tronic effects. Cis-trans isomerization (CTI) therefore exists in non-re-bonded or overcrowded molecules that switch from a given stable conformational state to another. This is the case of biaryl compounds which have been utilized in organic chemistry as the basis of molecular switches and rotors [1,2]. Nature has also exploited CTI of single bonds to increasing molecular diversity, in particular with the bulky thyroxin, a thyroid hormone, and the well-known disulfide bond which plays a critical role in the structure of peptides and in the conformation of proteins. 

Sandler, B. et al. 2004. Thyroxine-thyroid hormone receptor interactions. Journal of Biological Chemistry 279 55801-55808. 

Wolford, S. T., R. A. Schroer, F. X. Gohs, P. P. Gallo, H. B. Falk, and A. R. Dente. 1988. Effect of age on serum chemistry profile, electrophoresis and thyroid hormones in beagle dogs two weeks to one year of age. Veterinary Clinical Pathology 17 35-42. 

Jorgensen EC. Thyroid hormones. In Wolff ME, ed. Burger s Medicinal Chemistry, Part 3. 4th Ed. New York Wiley, 1981 103-148. 

L. G., and Gillner, M. (1998) Pharmacophores incorporating numerous excluded volumes defined by X-ray crystallographic structure in three-dimensional database searching application to the thyroid hormone receptor. Journal of Medicinal Chemistry,... 

Whereas some of the recent advances in thyroid function tests have been necessitated by the new concepts of thyroid hormone physiology, others have been secondary to major technological advances in clinical chemistry, in particular the introduction of radioimmunoassay (RIA). 

The reasons for briefly discussing PBI techniques in this review are minimal except for the fact that many automated units are still operating and because a PBI determination is sometimes useful in conjunction with other tests in delineating the site of a biosynthetic block in thyroid hormone synthesis. The subject was last reviewed in the series Advances in Clinical Chemistry by Chaney (C6) in 1958, and probably the most recent review is by Acland in 1971 (A4). 

Normal healthy adult male volunteers (10 per group) were then given 500 ml of water containing chlorine dioxide, chlorite, chlorate, chlorine or chloramine at 0 or 5 mg/l daily for 12 weeks. If one assumes a mean body weight of 70 kg, the dose of chlorite was equivalent to 0.036 mg/kg bw per day. Examinations included serum chemistry, blood count, urinalysis, special tests (e.g. thyroid hormones. 

Apart from surgery, blocking of the biosynthesis of the thyroid hormones is of particular interest. There are several hundred thionamides known, which exert their activity by inhibiting thyroperoxidase, an enzyme required for iodination and coupling of the tyrosine residues. However, only a few of these drugs are approved and in clinical use. Their synthesis employs conventional heterocyclic chemistry. 

Although radioiodinated antibodies have acceptable stability for in vitro applications, their in vivo stability is less ideal These tracers can act as substrates for the iodotransferase enzymes which are normally responsible for metabo lism of the thyroid hormones thyroxine and tri-iodothyronine which bear structural similarities. Although not present in the vascular circulation, these enzymes are widely distributed in many tissues and their action results in the intracellular release of the radionuclide which then either diffuses or is actively transported out of the cell and subsequently excreted in the urine. In order to try and increase the in vivo stability of antibodies labelled with radioiodine, alternative synthetic strategies have been pursued which result in molecules which are not substrates for the iodotransferases (11. 12). AU of these techniques are more complicated than the electrophilic substitution methods described above and require some synthetic chemistry in order to prepare the precursors which are not commercially available. 

K.V. Waite, G.F. Maberly, and C.J. Eastman, Storage conditions and stability of thyrotropin and thyroid hormones on filter paper, Clinical Chemistry 33(6) 853-855(1987). 

Tests to exclude possible causes of dementia include a depression screen, vitamin B12 deficiency, thyroid function tests [thyroid-stimulating hormone (TSH) and free triiodothyronine and thyroxine], complete blood cell count, and chemistry panel.21... 

Thyrotropinreleasing factor TRF receptor 3-residue peptide amide Stimulates thyroid-stimulating hormone and prolactin secretion Solid-phase A -Boc chemistry... 

Joliot-Curie, Frederick. (1900-1958). A French physicist who, along with his wife Irene Joliot-Curie, won the Nobel Prize in chemistry in 1935. His important discoveries included artificial radioactivity. He did much work on atom structure, dematerialization of electrons, and inverse transformation. Work on hormone synthesis and thyroid substances containing radioactively labeled elements was significant. ScD from the University of Paris was followed by a distinguished career filled with honors and appointments. 

Ismail, A.A., Walker, P.L., Barth, J.H., Lewandowski, K.C., Jones, R., and Burr, W.A. (2002) Wrong biochemistry results two case reports and observational study in 5310 patients on potentially misleading thyroid stimulating hormone and gonadotropin immu noassay results. Clinical Chemistry, 48, 2023 2029. 

Xu, Y.Y., Pettersson, K., Blomberg,K., Hemmila, I., Mikola, H., and Lovgren, T. (1992) Simultaneous quadruple label fluorometric immunoassay of thyroid stimulating hormone, 17 a hydroxyprogesterone, immunoreactive trypsin, and creatine kinase MM isoenzyme in dried blood spots. Clinical Chemistry, 38, 2038 2043. 

Thyroid. Tirotdina Thyradin Thyrocrine. Thyroid gland of domesticated animals that are used as food by man, freed from connective tissue and fat, dried and powdered. Contains not less than 0.17% and not over 0.23% iodine in thyroid combination. ] part — approx 5 parts fresh gland. Chemistry and physiology Rawson er of.. The Hormones vnl. Ill (Academic Press, New York, 1955) pp 433-519. 

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