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Enzymatic 5'-deiodination of T4 in various tissues is known to be stimulated by thiols and inhibited by propylthiouracil (PTU). Dithiothreitol (DTT) stimulation of rat kidney T4 5'-deiodinase followed saturation kinetics. Inhibition of the enzyme by PTU (10 (-5) M) was overcome in a concentration-dependent manner by DTT, methimazole (MMI), and thiourea. Pretreatment of catalytically active kidney microsomal preparations with PTS caused persistent inhibition of enzyme activity, assayed in the absence of PTU. Similarly, injection of PTU in rats in a dosage of 5 microgram/100 g BW or greater significantly impaired T4 5'-deiodination in subsequently isolated kidney microsomal preparations. Reagents that cleave disulfide bonds (DTT and KCN), as well as the reductant, Na2S2O4, and the thioureylene, MII, partially restored activity to PTU-inactivated enzyme in a time- and concentration-dependent way. These observations suggest that PTU inhibition of T4 5'-deiodinase results from an interaction of PTU with the enzym, possibly via a PTU-enzyme disulfide which can be prevented or reversed by thiols or thioureylene agents, and raise the possibility that protein sulfhydryl groups may undergo oxidation during the reductive 5'-deiodination of L-T4.
Leonard et al. (Fri,) studied this question.