Thyroxine-binding

Only small amounts of free T are present in plasma. Most T is bound to the specific carrier, ie, thyroxine-binding protein. T, which is very loosely bound to protein, passes rapidly from blood to cells, and accounts for 30—40% of total thyroid hormone activity (121). Most of the T may be produced by conversion of T at the site of action of the hormone by the selenoenzyme deiodinase (114). That is, T may be a prehormone requiring conversion to T to exert its metaboHc effect (123). 

Blake, C.C.F., et al. Structure of human plasma prealbumin at 2.5 A resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding. J. Mol. Biol. 88 1-12, 1974. 

Some hydroxy metabolites of coplanar PCBs, such as 4-OH and 3,3 4,5 -tet-rachlorobiphenyl, act as antagonists of thyroxin (Chapter 6, Section 6.2.4). They have high affinity for the thyroxin-binding site on transthyretin (TTR) in plasma. Toxic effects include vitamin A deficiency. Biomarker assays for this toxic mechanism include percentage of thyroxin-binding sites to which rodenticide is bound, plasma levels of thyroxin, and plasma levels of vitamin A. 

D24. Docter, R., van Toor, H., Krenning, E. P., de Jong, M., and Hennemann G., Free thyroxine assessed with three assays in sera of patients with nonthyroidal illness and of subjects with abnormal concentrations of thyroxine-binding proteins. Clin. Chem. 39,1668-1674 (1993). 

The thyroid hormones are lipophilic and relatively insoluble in the plasma. Therefore, they are transported throughout the circulation bound to plasma proteins such as thyroxine-binding globulin (75%) and albumins (25%). Approximately 99.96% of circulating thyroxine is protein bound. Bound hormone is not available to cause any physiological effects however, it is in equilibrium with the remaining 0.04% that is unbound. This free form of the hormone is able to bind to receptors on target tissues and cause its effects. Thyroid hormone has many metabolic effects in the body ... 

Thyroxine binding globulin 0.01-0.02 58 Binds/transports thyroxine... 

Brouwer, A., E. Klasson-Wehler, M. Bokdam, D.C. Morse, and W.A. Traag. 1990. Competitive inhibition of thyroxin binding to transthyretin by monohydroxy metabolites of 3,3, 4,4 -tetrachlorobiphenyl. Chemo-sphere 20 1257-1262. 

Estrogen may increase hepatic production of thyroxine-binding globulin (TBG) and decrease TBG clearance, thus increasing serum total thyroxine (tT4) and, to a lesser extent, total triiodothyronine (tT3). As a result, increased tT4 and tT3 are seen in states of excessive estrogen and/or progestin, such as... 

Duntas LH, Mantzou E, Koutras DA (2001) Lack of substantial effects of raloxifene on thyroxine-binding globulin in postmenopausal women dependency on thyroid status. Thyroid 11 779-782... 

The basis for this technique lies in the competition between the test antigen and a labelled antigen for the available binding sites on a fixed amount of antibody. While the binding sites are traditionally associated with an antibody, any source of specific reversible binding sites may be used to create an assay in this format. Examples of such are specific transport proteins such as thyroxine-binding globulin and certain cellular receptors such as opiate or benzodiazepine receptors. Under these circumstances the equilibrium mixture may be represented thus ... 

PAGE Poiyacryiamide gei eiectropho- TBG Thyroxine-binding globulin... 

Animal studies have shown that the immune system is sensitive to exposure. Mice fed diets containing 50 or 5 00 ppm technical-grade pentachlorophenol showed greatly reduced immunocompetence in the form of increased susceptibility to the growth of transplanted tumors. Oral and intraperitoneal administration to animals causes adverse effects on thyroid homeostasis and on the thyroid gland. Competition for serum protein thyroxine binding sites may account for the antithyroid effects of pentachlorophenol. ... 

P5. Pensky, J., and Marshall, J. S., Studies on thyroxine-binding globulin (TBG)... 

Thyroid function tests - Decreased levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, and there is no... 

Thyroxine-binding globulin is the least abundant of the three major transport proteins. Nevertheless, it carries about 70% of the circulating T4 and Tj by virtue of its high affinity for the two hormones. Transthyretin, formerly known as thyroxine-binding prealbumin, binds only about 10 to 15% of the hormones. Albumin, a protein that has a binding affinity for a multitude of small molecules, has an even lower affinity for T4 and T3 than... 

The iodothyronines are very insoluble molecules and are kept in solution by transport proteins. The most important of these is thyroxine binding globulin (TBG), which carries about 65% T and 70% Tj. It is a small (MW 60,000-65,000) glycoprotein consisting of four subunits. It has a single, high-affmity binding site for T, with an estimated of 1.2 x 10 °M. 

Thyroxine binding prealbumin (TBPA) carries about 30% T but no Tj. Its affinity is only of the order of 10 M, but it is much more abundant in semm than is TBG. The amino acid sequence and the structure of this protein are known. Four identical subunits (127 amino acids each) form a prolate ellipsoid. Noncovalent interactions between the subunits form a channel of I nm diameter along the long axis, which has a funnel-shaped opening of 2.5 nm. The T molecule is held in one arm of this channel, binding... 

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