Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin
article
Previous results (Brouwer and van den Berg, Toxicol. Appl. Pharmacol., 85 (1986) 301) indicated preferential binding of a hydroxylated metabolite of tetrachlorobiphenyl to transthyretin (TTR) a carrier of thyroxine (T4). In the present study it was investigated whether the T4 binding site of TTR could be occupied specifically by hydroxylated chlorinated aromatic compounds using chlorinated phenol congeners as model compounds in a competition assay with [125I]T4. Chlorinated aromatics such as 2,3-dichlorobenzene and 3,4,3',4'-tetrachlorobiphenyl, and phenols such as 4-hydroxybiphenyl and phenol were inefficient competitors. All chlorinated phenols tested were competitors for the T4 binding site of TTR. The ranking in competition was pentachlorophenol (PCP) > trichlorophenols > dichlorophenols > monochlorophenols. Structures with chlorine in both ortho positions to the hydroxyl group were more efficient competitors. The relative affinity of binding of pentachlorophenol (PCP) to TTR was about twice that of T4. Scatchard analysis showed that PCP mainly decreased the affected constant K11 while the binding capacity R1 was not altered, indicating a competitive type of inhibition. PCP was also able to compete with T4 sites on albumin with a relative affinity of 0.25. T4 binding to thyroid binding globulin (TBG) was much less affinity by interference of PCP (relative affinity 0.001). The results indicate a specific interaction of chlorophenols with the T4 binding site of TTR.
Topics
AlbuminChlorophenolsPentachlorophenolThyroid binding globulinThyroxine binding siteTransthyretinRadioisotopeThyroxineThyroxine binding globulinThyroxine binding proteinNonhumanPriority journalScatchard plotBinding SitesBinding, CompetitiveChemistryChlorophenolsHumanPrealbuminReceptors, Thyroid HormoneSerum AlbuminThyroxine
TNO Identifier
231218
ISSN
00092797
Source
Chemico-Biological Interactions, 76(1), pp. 63-75.
Pages
63-75
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