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Propylthiouracil (PTU) and iodoacetate (IAc) partially inhibit the 5'-deiodination of 3,3',5'-triiodothyronine (rT3) in cerebral cortex, but PTU has no effect on the 5'-deiodination of thyroxine (T4). We now report that pretreatment of cerebral cortex microsomes with increasing concentrations of IAc or iodoacetamide inhibits the PTU-sensitive 5'-deiodination of rT3 with half-maximal inhibition at less than 1 microM IAc. PTU-insensitive 5'-deiodination of rT3 and T4 requires 100-1000-fold higher concentrations of IAc to achieve similar inhibition. Trypsinization decreases both 5'-deiodinating activities by greater than 90%. These data suggest that enzyme SH groups do not participate in the 5'-deiodination of T4 or rT3 by the PTU-insensitive pathway.
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