The integrity of the ether linkage during thyroxine metabolism in man.

The structures of thyroxine metabolites after total deiodination bear on the mode of thyroxine (T(4)) action in vivo. The present study was undertaken to determine the integrity of the ether linkage during thyroxine metabolism in man. Normal volunteers were given simultaneous intravenous injections of two thyroxines labeled with either (14)C or (3)H on the opposite sides of the ether linkage, D,L-[alpha,beta-(3)H]T(4) and D,L-[phenolic ring-(14)C]T(4). The ratio of alanine side chain to phenolic ring which was measured as (3)H:(14)C ratio was found to remain constant in the serum, urine, and feces during the subsequent 3 wk. The disappearance rates of the (3)H and (14)C radioactivity from blood were similar. The values of half-life were in the ranges of 4.2-6.7 days. 51-63% of the (3)H and 50-57% of the (14)C doses were recovered from urine and 13-20% of the (3)H and 15-20% of the (14)C doses were recovered from feces. Chromatography of the urinary metabolites confirmed that the phenolic ring and the nonphenolic ring including at least part of the side chain remained linked together.