64192-57-0Relevant academic research and scientific papers
Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics
Butt, Craig M.,Stapleton, Heather M.
, p. 1692 - 1702 (2013)
Many halogenated organic contaminants (HOCs) are considered endocrine disruptors and affect the hypothalamic-pituitary-thyroid axis, often by interfering with circulating levels of thyroid hormones (THs). We investigated one potential mechanism for TH dis
Halogen bonding controls the regioselectivity of the deiodination of thyroid hormones and their sulfate analogues
Manna, Debasish,Mondal, Santanu,Mugesh, Govindasamy
supporting information, p. 2409 - 2416 (2015/01/30)
The type 1 iodothyronine deiodinase (1D-1) in liver and kidney converts the L-thyroxine (T4), a prohormone, by outer-ring (5′) deiodination to biologically active 3,3′,5-triiodothyronine (T3) or by inner-ring (5) deiodination to inactive 3,3′,5′'-triiodothronine (rT3). Sulfate conjugation is an important step in the irreversible inactivation of thyroid hormones. While sulfate conjugation of the phenolic hydroxyl group stimulates the 5-deiodination of T4 and T3, it blocks the 5′-deiodination of T4. We show that thyroxine sulfate (T4S) undergoes faster deiodination as compared to the parent thyroid hormone T4 by synthetic selenium compounds. It is also shown that ID-3 mimics, which are remarkably selective to the inner-ring deiodination of T4 and T3, changes the selectivity completely when T4S is used as a substrate. From the theoretical investigations, it is observed that the strength of halogen bonding increases upon sulfate conjugation, which leads to a change in the regioselectivity of ID-3 mimics towards the deiodination of T4S. It has been shown that these mimics perform both the 5′- and 5-ring deiodinations by an identical mechanism.
