A prealbumin variant with an increased affinity for T4 and reverse-T3.
A euthyroid adult female (LC) was found to have persistently raised concentrations of total T4 (159 nmol/l) and rT3 (500 pmol/l) in her serum in association with a normal T3 (2.1 nmol/l). Serum concentrations of all three T4-binding proteins were within normal limits. A variant prealbumin with an increased affinity for T4 was found to be responsible for the raised serum level of T4. Unlike normal prealbumin, the variant also bound appreciable amounts of rT3. The affinity constant for T4 binding to prealbumin LC was 5.5 X 10(8) l/mole which is sevenfold higher than that obtained for normal prealbumin (8.5 X 10(7) l/mole). The affinity constant for the binding of rT3 to prealbumin LC was 2.0 X 10(6) l/mole while that for the normal protein was unmeasurable by our method. The T4-binding capacity of prealbumin LC in serum was within the normal range indicating that there is no new additional T4-binding site on the protein. Prealbumin LC has the same molecular size as the normal protein, hence it is likely that the tetrameric structure has been preserved. The electrophoretic mobility of prealbumin LC was normal indicating no alteration in charge. It is postulated that the increased affinity for T4 (and presumably for rT3) results from a hydrophobic amino-acid substitution in the prealbumin monomer.
D000328:Adult; D004590:Electrophoresis, Paper; D005260:Female; D006801:Humans; D011228:Prealbumin / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013974:Thyroxine / Q000097:blood*; D013975:Thyroxine-Binding Proteins / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood*
D011228:Prealbumin; D012709:Serum Albumin; D013975:Thyroxine-Binding Proteins; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D013974:Thyroxine