When activated by dithiothreitol, iodothyronine 5'-deiodinase (I-5'D) activity 
in kidney microsomes is less sensitive to inhibition by propylthiouracil (PTU) 
and iopanoate (IOP) at nanomolar, compared to micromolar, substrate 
concentrations. The enzymatic activities at nanomolar substrate concentrations 
are, however, completely eliminated in the presence of a combination of 10 
microM IOP and 100 microM PTU. In this report we present evidence that 1) the 
relative PTU insensitivity results from the residual activities of the high Km 
enzyme which, while being very sensitive to PTU inhibition at micromolar 
substrate concentrations, becomes progressively less PTU sensitive as substrate 
concentrations decline relative to its Km; and 2) the relative IOP insensitivity 
is due to the presence in kidney microsomes of a low Km enzyme which is 
relatively insensitive to IOP, but highly sensitive to inhibition by PTU. 
Classifying the deiodinases on the basis of PTU sensitivity, therefore, requires 
that not only the thiol concentrations, but, as in the case of the type I 
enzyme, also the substrate concentrations be specified. The PTU resistance of 
the type I enzyme at nanomolar substrate concentrations suggests a role of this 
enzyme in T3 neogenesis in PTU-treated animals.