The contribution of thyroxine-binding prealbumin to the binding of thyroxine in human serum, as assessed by immunoadsorption

Abstract

A B S T R A C T An immunoadsorption technique employing a rabbit antiserum specific for human serum prealbumin has been devised to remove thyroxine (T4)-binding prealbumin (TBPA) from serum completely without affecting the T4 -binding activity of thyroxine-binding globulin (TBG) or the concentration of the other major proteins in serum. As judged from the proportion of T4 associated with the antigen-antibody precipitate, only about 15% of the endogenous T4 is bound by TBPA, a value considerably less than that indicated by electrophoretic methods. As judged from the increase in the proportion of free T4 that followed immunoadsorption of TBPA, TBPA does act as one determinant of the proportion of free T4 but is far less important than TBG in this respect. A decrease in the T4-binding capacity of TBPA cannot solely account for the increase in the proportion of free T4 in the sera of ill patients, since a comparable increase does not occur in normal sera after complete removal of TBPA. From data obtained in normal and abnormal sera before and after immunoadsorption of TBPA, estimates of the equilibrium constants for the interactions between T4 and its binding proteins, as they exist in serum, have been derived.

Aboard transthyretin: From transport to cleavage

“…Together, the studies referred above suggest that the relevance of TTR is more than that initially described, as a carrier of T 4 and retinol. Throughout time, studies addressing the identification of novel TTR ligands were performed to explore the biology of the protein.…”

“…In the case of TTR, studies with TTR knockout (KO) mice suggested that TTR is not required for normal T 4 tissue uptake or distribution, and that its absence does not impair hormone tissue contents, despite the low circulating levels of total T 4 (16,17). These observations reinforced the idea that TTR is not necessary for the metabolism of T 4 and are in agreement with the free hormone hypothesis for T 4 uptake (18), in which the hormone biological activity depends only on its free plasma concentration. On the other hand, it was reported that T 4 distribution from the CSF into the brain is TTR-dependent and occurs via receptor-mediated endocytosis (19).…”

“…As referred above, TTR most studied role is the transport of T 4 and retinol. As such, these ligands will be the first described in this review.…”

“…In the CSF, TTR is the major T 4 carrier of both rodents and humans. At the structural level, two identical binding sites for T 4 are located in the central channel of the TTR tetramer (14). As the two T 4 binding sites present negative cooperativity (15), each TTR tetramer carries no more than one T 4 molecule.…”

Modeling Amyloid Diseases in Fruit Fly Drosophila Melanogaster

“…Transthyretin (TTR), plasma protein primarily synthesized in the liver, choroid plexus and in retinal pigment epithelium, is the basic transporter of thyroxine and retinol-binding protein in mammals [Goodman, D., 1987;Woeber & Ingbar, 1968]. Three human diseases are characterized by extracellular transthyretin deposits -Familial Amyloidotic Polyneuropathy (FAP), Familial Amyloidotic Cardiomyopathy (FAC) and Senile Systemic Amyloidosis (SSA).…”