Rapid Deiodination of Triiodothyronine Sulfate by Rat Liver Microsomal Fraction

Triiodothyronine sulfate (T3S) was synthetized chemically, and reacted at 37 C and pH 7.2 with rat liver microsomes and 5 mM dithiothreitol (DTT). The production of 3,3′-diiodothyronine sulfate (3,3′-T2S) from unlabeled T3S was measured after hydrolysis with a specific 3,3′-T2 radioimmunoassay, and the production of radioactive I- from outer ring-labeled T3S by ion-exchange chromatography. Production of both 3,3′-T2S and I- was DTT dependent, strongly inhibited by 6-propyl-2-thiouracil (PTU), and abolished after heat-inactivation of the microsomes. The time sequence and enzyme dependence of product formation suggested that most if not all I- was produced via 3,3′-T2S. Inner ring deiodination of T3S was two orders of magnitude faster than that of T3 as the result of a lower apparent Km (4.6 vs 10.7 μM) and a markedly increased Vmax (1050 vs 33 pmol/mg protein·min). It is postulated that T3S is a key intermediate in the metabolism of T3.