Abstract
The characteristics of thyroxine (T4) deiodination to 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) and of each of the latter to 3,3'-diiodothyronine (3,3'T2) were examined in rat liver homogenate. Each of the four reactions was enzymatic in nature, demonstrating pH and temperature optima, and tissue and time dependence. All reactions were considerably augmented (greater than 10-fold) by the presence of a thiol agent. At pH 7.2 with 2 muM T4 as substrate, rT3 generation was 3.3 +/- 0.44 (S.E.) and T3 formation was 4.8 +/- 0.57 pmol/min/100 mg of homogenate protein. Fasting for 72 h resulted in a significant inhibition of T4 deiodination, compared to that in the glucose-fed animals, in a 2% homogenate preparation. Enzyme activity for T4 to T3 was reduced by 54% (p less than 0.05) in the homogenate from the fasted rats. Fasting lowered the enzyme activity of T4 to rT3 by 56% (p less than 0.05). Although the monodeiodination of T3 to 3,3'-T2 was also significantly depressed (p less than 0.01) by fasting, rT3 deiodination to 3,3'-T2 was not. The in vitro additon of 5 mM dithioerythritol did not reverse the effect of fasting on any reaction. These results demonstrate that a 72-h fast significantly impairs the sequential deiodination of T4 in liver homogenate. The effect of fasting appears to be mediated mainly through a reduction in enzyme concentration rather than co-factor availability.
Highlights
From the Endocrine, Medical, and Nuclear Medicine Services, Veterans Administration Medical Center, and the Department of Medicine and Radiology, University of California at Sun Francisco, Sun Francisco, California 94102
Deiodination of both triiodothyronines,with the formationof. These results demonstrate that a72-h fast signifi- 3,3’-diiodothyronine (3,3”Tn)as a common product, accounts cantly impairs the sequential deiodination of T4in liver homogenate
Deiodination-Table I shows the results of experiments in which the generation of TBand 3,3’-T2from Tq as substrate was studied in liver homogenates from rats either fasted for 72 h or fed 20%glucose in drinking water as the only source of food for the same period
Summary
(Received for publication,March 20, 1979, and in revised form, September 10, 1979). From the Endocrine, Medical, and Nuclear Medicine Services, Veterans Administration Medical Center, and the Department of Medicine and Radiology, University of California at Sun Francisco, Sun Francisco, California 94102. Tracer studies have shown that the formationof rT. from T4 is a major pathway of thyroxine metabolism [12, 13] and is unchanged or only slightly increased during caloric deprivation [3, 14]. It is not knownwhichtissues contributeto rTa formation under such circumstances. These results demonstrate that a72-h fast signifi- 3,3’-diiodothyronine (3,3”Tn)as a common product, accounts cantly impairs the sequential deiodination of T4in liver homogenate. Other chemicals used were reagent grade and were purchased from commercial suppliers
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