A possible function of thiols, including glutathione, as cofactors in the conversion of thyroxine to 3,3',5-triiodothyronine in rat liver microsomes

Abstract

Thyroxine (T4) is known to be converted to triiodothyronine (T3) in rat liver microsomes. An endogenous stimulatory factor for the conversion of T4 to T3 was identified as reduced glutathione (GSH) by Sephadex G-15 gel chromatography of rat liver extract. The production of T3 in rat liver microsomes was maximally stimulated above a GSH concentration of 4mM, and an approximately 5-fold stimulation was attained. This degree of stimulation was approximately 10 time less than that observed with dithiothreitol (DTT). Activity in the conversion of T4 to T3 was solubilized from the microsomes using 0.1% deoxycholate. When the solubilized microsomal preparation, pre-treated with DTT or GSH, was subjected to gel filtration on a Sepharose CL-6B column to separate the preparation from the thiol, almost no T3 producing activity was observed in any of the collected fractions. However, when DTT or GSH was added to the fractions containing high molecular weight components, the activity of the production of T3 was sustained. This finding indicates that these thiols play an essential role in the conversion of T4 to T3, possibly acting as cofactors.