title: The thyroxine-binding proteins.
abstract: The slow clearance, prolonged half-life, and high serum concentration of thyroxine (T4) are largely due to strong binding by the principal plasma thyroid hormone-binding proteins, thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin. These proteins, which shield the hydrophobic thyroid hormones from their aqueous environment, buffer a stable free T4 concentration for cell uptake. Free rather than bound T4 is subject to homeostatic control by the hypothalamic-pituitary thyroid axis. Although it is not a protease inhibitor, sequence analysis identifies TBG as a member of the serine protease inhibitor (serpin) family of proteins. Proteolytic cleavage of TBG appears to be a mechanism for site-specific release of T4 independently of homeostatic control. TBG probably facilitates the transport of maternal T4 and iodide to the fetus, although this remains to be proven. High-affinity cellular binding sites for TTR have been described; however, their function and that of choroid plexus synthesis of TTR and transport of T4 into the cerebrospinal fluid remain unclear. Albumin, with the lowest T4 affinity and fastest T4 release of the major T4-binding proteins may promote quick exchange of T4 with tissue sites. The affinity of albumin for T4 is increased by histidine substitution for arginine 218 in the most common form of dysalbuminemic hyperthyroxinemia. However, proline and alanine substitutions at the same site have a similar effect, suggesting that arginine 218 interferes with T4 binding.
authors.affiliation: State University of New York Health Science Center, Brooklyn 11203, USA. George.C.Schussler-New-York@worldnet.att.net
authors.forename: G C
authors.initials: GC
authors.lastname: Schussler
mesh_terms: D000375:Aging / Q000097:blood; D000818:Animals; D005260:Female; D006509:Hepatitis B / Q000097:blood; D006801:Humans; D008958:Models, Molecular; D011228:Prealbumin / Q000378:metabolism; D011247:Pregnancy / Q000097:blood / Q000378:metabolism; D013974:Thyroxine / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000032:analysis
chemical_list: D011228:Prealbumin; D013975:Thyroxine-Binding Proteins; D013974:Thyroxine