Thyroid hormone-prealbumin

Burridge, and C. C. F. Blake, ]. Med. Chem., 25, 785 (1982). Computer Graphics in Drug Design Molecular Modelling of Thyroid Hormone—Prealbumin Interactions. 

Thyroxine (3, 5, 3,5-L-teraiodothyronine, T4) is a thyroid hormone, which is transformed in peripheral tissues by the enzyme 5 -monodeiodinase to triiodothyronine. T4 is 3-8 times less active than triiodothyronine. T4 circulates in plasma bound to plasma proteins (T4-binding globulin, T4-binding prealbumin and albumin). It is effective in its free non-protein-bound form, which accounts for less than 1%. Its half-life is about 190 h. 

Thyroid hormone is liberated into the bloodstream by the process of proteolysis within thyroid cells. T4 and T3 are transported in the bloodstream by three proteins thyroid-binding globulin, thyroid-binding prealbumin, and albumin. Only the unbound (free) thyroid hormone is able to diffuse into the cell, elicit a biologic effect, and regulate thyroid-stimulating hormone (TSH) secretion from the pituitary. 

Transport. A wellknown transport protein is hemoglobin in the erythrocytes (bottom left). It is responsible for the transport of oxygen and carbon dioxide between the lungs and tissues (see p.282). The blood plasma also contains many other proteins with transport functions. Prealbumin (transthyretin middle), for example, transports the thyroid hormones thyroxin and triiodothyronine. Ion channels and other integral membrane proteins (see p.220) facilitate the transport of ions and metabolites across biological membranes. 

The concentration of free rather than bound thyroxine is considered to be the most accurate assessment of thyroid activity as this is the fraction which can penetrate cell membranes and exert a metabolic effect. Free thyroxine exists in equilibrium with thyroxine bound to globulin, albumin, and prealbumin. Any changes in the concentration of thyroid binding proteins leading to an increase in free hormone. Thyroid binding prealbumin is reduced after all kinds of stress and the reduction is significant within 24 hours. 

Thyroid hormones have a lengthy life-span in the bloodstream — several days — probably because they are bound to proteins in the circulation. More than of T4 and T3 is bound to plasma proteins. These prolerns arc thyroid hormone-binding protein, transthyretin, and albumin. Most of the hormone is carded by thyroid hormone-binding protein. Transthyretin (from thyroid and retinol) occurs in a Irl complex with retinol-binding protein In the bloodstream. This complex serves to prevent the loss of retinol-binding protein, which is a small protein, in the urine. Transthyretin has also been called prealbumin, it binds T4 and not TJ,... 

Transthyretin (prealbumin) and retinol-binding protein (RBP) are transport proteins that migrate together as a 1 1 molecular complex. Transthyretin was originally named prealbumin because of its electrophoretic mobility it was renamed in 1981 to reflect its binding and transport of both thyroid hormones (thyroxine and triiodothyronine) and RBP. 

Ingbar, 8. H., Observations concerning binding of thyroid hormones by human serum prealbumin. J. Clin. Invest. 42, 143-160 (1963). 

Larsson, M., T. Pettersson, and A. Carlstrom. 1985. Thyroid hormone binding in serum of 15 vertebrate species Isolation of thyroxine-binding globulin and prealbumin analogs. General Comparative Endocrinology 58 360-375. 

Human prealbumin is involved in the transport of thyroid hormones in plasma. V-Bromoacetyl-L-thyroxine [BrAcT4 (II) in Scheme 2], an analog of L-thyroxine [T4 (I) in Scheme 2], differs from T< only in the... 

RBP interacts strongly with another protein, plasma transthyretin (TTR, also more commonly referred to as plasma prealbumin) and normally circulates as a 1 1 molar RBP-TTR complex. [The name transthyretin has been suggested (Nomenclature Committee of lUB et al., 1981) for the protein usually called prealbumin and will be used instead of the term prealbumin in this and other chapters.] The usual level of RBP in plasma is about 40-50 p,g/ml and that of TTR is about 200-300 pg/ml. In addition to its role in vitamin A transport, TTR plays a role in the binding and plasma transport of thyroid hormones. The formation of the RBP-TTR complex serves to reduce the glomerular filtration and renal catabolism of RBP. 

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