The substrate specificity, tissue specificity and regulation of the 5' deiodination systems in rat liver and kidney tissues.
Studies were carried out to compare the 5' deiodination reactions of thyroxine (T4) and 3, 3', 5'-triiodothyronine (rT3) in rat liver and kidney homogenates. The 5'-deiodinase activity was assayed by the 3, 5, 3'-triiodothyronine (T3) produced from T4 or by the 125I-iodide released from 125I-rT3. The two 5' deiodination reactions had similar ranges of optimal pH, incubation temperature, and apparent Km, T4 1.1 and rT3 1.3 microM. However, the apparent Vmax values for T4 and rT3 deiodination reactions were 0.9 and 220 pmol/mg protein/min, respectively. Both reactions were stimulated by thiol reagent but only rT3 deiodination showed complete thiol dependence. The inhibitory effect of 6-propyl-2-thiouracil (PTU) on the 5' deiodination of rT3 was 50 times as great as that of T4. Only the 5' deiodination of rT3 was inhibited by low concentrations of calcium and magnesium. The 5' deiodination reactions in the liver and kidney tissues showed very similar substrate specificity. However, only the hepatic deiodinase activity was reduced to 60-65% of the control value after fasting, whereas the renal 5'-deiodinase activity was unaffected or even enhanced by fasting up to 72 hours. The results showed the existence of a diverse and complex 5' deiodination system in the rat tissues which is comprised of multiple similar but distinct 5'-deiodinase enzymes with respect to their substrate specificity, tissue specificity and regulation.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D004793:Enzyme Reactivators / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007453:Iodide Peroxidase / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009928:Organ Specificity; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D013696:Temperature; D013974:Thyroxine / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism; D014285:Triiodothyronine, Reverse / Q000378:metabolism
D004793:Enzyme Reactivators; D007457:Iodine Radioisotopes; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D011441:Propylthiouracil; D007453:Iodide Peroxidase; D008274:Magnesium; D013974:Thyroxine; D002118:Calcium