Effects of glutathione on iodothyronine 5'-deiodinase activity.
At nanomolar substrate levels, physiological concentrations (less than or equal to 5 mM) of glutathione (GSH) activate a low Km iodothyronine 5'-deiodinase (I-5'D) activity in renal and hepatic microsomes, but not the low Km (type II) I-5'D in the pituitary, cerebral cortex, or brown adipose tissue. The latter enzyme as well as the type I enzyme activity at micromolar substrate concentrations required higher (greater than 10 mM) concentrations of GSH. However, GSH appeared to interact with the type I and type II enzymes even at subactivation levels, since it inhibited the activation of these enzymes by dithiothreitol (DTT). Activation of the renal and hepatic low Km I-5'D by GSH resembled that by DTT in 1) the similarity of Km values for both T4 (20 nM) and rT3 (2 nM), 2) the catalytic mechanism (ordered sequential with the iodothyronine as the second substrate), 3) the values for activation energies, and 4) sensitivity to inhibition by propylthiouracil. However, the low Km I-5'D activated by GSH was about 10-fold more sensitive to inhibition by iopanoate than when activated by DTT. The responsiveness of the low Km I-5'D's in renal and hepatic microsomes to physiological concentrations of GSH suggests their participation in the metabolism of iodothyronines in vivo.
Goswami
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Department of Medicine, Framingham Union Hospital, Massachusetts 01701.
Rosenberg
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D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D054477:Glutaredoxins; D005978:Glutathione / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D013816:Thermodynamics
D001426:Bacterial Proteins; C516010:Glrx2 protein, rat; D054477:Glutaredoxins; D011506:Proteins; D010088:Oxidoreductases; D007453:Iodide Peroxidase; D005978:Glutathione; D004229:Dithiothreitol