Iodothyronine 5'-deiodination in rat kidney microsomes: sensitivity to propylthiouracil.
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.
Goswami
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Department of Medicine, Framingham Union Hospital, Massachusetts 01701.
Rosenberg
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D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007480:Iopanoic Acid / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D014285:Triiodothyronine, Reverse / Q000378:metabolism
D014285:Triiodothyronine, Reverse; D011441:Propylthiouracil; D007453:Iodide Peroxidase; D007480:Iopanoic Acid; D004229:Dithiothreitol