Thyroid Hormone Structure-Activity Relationships: An Unusual Conformation for 3, 5, 3’-Triiodothyropropionic Acid

Abstract

Although the major metabolic reactions affecting the thyroid hormone alanine side chain are deamination and decarboxylation, there is a paucity of data concerning the physiological function of these reaction products, in particular the thyropropionic acid metabolites. In man it has been shown that 44% of labeled thyroxine is excreted as thyroacetic acids whose plasma half-times are considerably shorter than those of the parent compounds (1). This is in contrast to the observation that, despite their low hormonal potencies, the acetic acid metabolites are bound at least as strongly to rat liver nuclei and more so to the plasma proteins (2,3). However, at present there is no clear evidence for the formation of thyropropionic acids in human or animal tissues (4). The acid metabolites (formic, acetic, propionic) have been shown to bind more tightly to thyroxine-binding prealbumin and the type I deiodinase enzyme, than does the thyroid hormone thyroxine (T₄) (5,6).

Supported by the Kroc Foundation and NIH AM15051.