Formation of iodoprotein during the peripheral metabolism of 3,5,3'-triiodo-L-thyronine-125I in the euthyroid man and rat.

3,5,3'-Triiodo-L-thyronine-(125)I (T3-(125)I) metabolism was studied in nine euthyroid human subjects on blocking doses of nonradioactive iodide. After the intravenous injection of T3-(125)I, the fractional disappearance rate of plasma radioactivity progressively disappearance rate of plasma radioactivity progressively decreased with time. Analysis of individual plasma samples by dialysis, electrophoretic, and extraction techniques revealed three radioactive components: T3-(125)I, iodide-(125)I, and an unidentified material which was nonextractable in acid butanol (NE(125)I). Ne(125)I rose to maximal levels 24-36 hr after injection of T3-(125)I and then decreased with a fractional rate which approached, after 12-14 days, approximately 0.05 day(-1) (t(1/2) = 14 days). The plasma T3-(125)I concentration, obtained by subtraction of iodide-(125)I and NE(125)I from the plasma total (125)I, declined at a constant fractional rate with time with a t(1/2) of 1.5 days. Qualitatively similar results were obtained in rats. After 72 hr, 57% of the plasma and 40% of the liver radioactivity was NE(125)I. Chromatographic purification of the T3-(125)I before injection did not alter these results. The extrathyroidal origin of NE(125)I was further demonstrated by similar results in thyroidectomized rats maintained on thyroxine. NE(125)I from human sera separated from the other radioiodinated substances by ion-exchange chromatography was quantitatively precipitated by trichloracetic acid, not dialyzable, insoluble in CHCl(3):CH(2)OH, and migrated with albumin during starch-gel electrophoresis. Based on these properties, NE(125)I was tentatively identified as iodoalbumin. Observations in rats equilibrated with (125)I, as well as nonradioactive iodine determinations in human sera before and after acid butanol extraction, indicate that 10-20% of the serum organic iodine is in the form of iodoprotein. Our studies suggest that this moiety may be derived at least in part from the peripheral metabolism of the thyroid hormones.