Thyroxine-prealbumin complex

Figure 28-21 Themoleculei-thyroxine. 7. binds to prealbumin, a protein found in blood. Based on x-ray data of the >-thyroxine-prealbumin complex, the binding affinity of novel analogues was prediaed by using a molecular modeling approach.

Fig. 2. A view of the thyroxine-prealbumin complex, with the arrow designating the naphthyl hole [31).

RBP forms a 1 1 complex with the tetrameric thyroxine-binding prealbumin, transthyretin. This is important to prevent urinary loss of retinol bound to the relatively small RBP (Mr 21,000), which would be filtered by the glomerulus transthyretin has an Mr of 54,000 hence, the complex will not normally be filtered, ffowever, moderate renal damage, or the increased permeability of the glomerulus in infection, may result in considerable loss of vitamin A bound to RBP-transthyretin. 

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. 

Transthyretin (also known as prealbumin) Liver plasma circulating form is a tetramer composed of four identical monomers. M.W. 55,000 1-2 days N 20-40 mg/dl Mild 10-15 mg/dl Moderate 5-10 mg/dl Severe <5 mg/dl Circulates in plasma in a 1 1 complex with retinol-binding protein, transports thyroxine, has a small body pool, and has a short half-life. Sensitive indicator of protein deficiency and in the improvement with protein refeeding. 

Figure 26. Prealbumin (blue) complexed with L-thyroxine (14a, red). The empty binding pocket is highlighted in yellow and a bound water molecule is shown in green.

In actual use, one projects an image of a receptor in one colour and of an agonist in another colour, with all van der Waals bonds in correct proportions, and rotates the receptor and drug images with respect to one another. When best fit has been achieved, one can rotate the complex to study various aspects of it. Coloured stereoptical pairs of photographs are now appearing in the literature, e.g. dihydrofolate reductase and its inhibitors (Hansch etaL, 1982). Thyroxine 11.14) whose reaction with its first receptor, prealbumin, was described in Section 2.4, can be seen, thus combined, in coloured stereoptics (Blaney 1982). 

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