- Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics
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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
- Butt, Craig M.,Stapleton, Heather M.
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- Halogen bonding controls the regioselectivity of the deiodination of thyroid hormones and their sulfate analogues
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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.
- Manna, Debasish,Mondal, Santanu,Mugesh, Govindasamy
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p. 2409 - 2416
(2015/01/30)
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