Dietary modification of thyroxine deiodination in rat liver is not mediated by hepatic sulfhydryls.
The enzymatic deiodination of thyroxine (T(4)) is thiol dependent. Fasting (72 h) depresses hepatic T(4) deiodination and lowers the hepatic content of nonprotein sulfhydryls (NP-SH) and reduced glutathione (GSH). It has been proposed that the fasting effect may be mediated through these alterations in hepatic sulfhydryls. To test the importance of tissue (hepatic) thiol content in the modification of T(4) deiodination consequent to dietary manipulation, we examined the sequential deiodination of T(4) to 3,5,3'-triiodothyronine (T(3)) (5'-deiodination) and 3,3',5-triiodothyronine (reverse T(3), rT(3)) (5-deiodination) in liver homogenates without added thiol from groups of rats fed Purina lab chow (P) (a protein-rich diet), glucose alone (G), or glucose plus cysteine (G(c)) for 72 h or fasted (F) for the same period. The initial rate of each reaction was compared to the tissue concentrations of NP-SH and GSH. Dietary manipulation induced significant changes in hepatic deiodination of T(4) to T(3) and rT(3) and sulfhydryl content. There was a marked dissociation between the rate of each reaction and hepatic NP-SH and GSH levels. T(4) deiodination by the alternative pathways was significantly higher (P < 0.01) in G > P > F. In contrast both hepatic NP-SH and GSH concentrations were greater (P < 0.05) in P > F > G. The lack of a relationship between these parameters was further emphasized on analysis of tissue from rats fed G(c). Despite the clearcut (P < 0.01) increase in hepatic NP-SH and GSH consequent to G(c) feeding, there was no alteration in iodothyronine deiodination compared to the group fed glucose alone. These data indicate that the effects of diet on T(4) monodeiodination in liver are not mediated by changes in the tissue level of sulfhydryl compounds but rather involve alterations in the concentrations of the deiodinases.
D000818:Animals; D001711:Biotransformation; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004032:Diet; D005215:Fasting; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000096:biosynthesis; D014285:Triiodothyronine, Reverse / Q000096:biosynthesis
D001786:Blood Glucose; D013438:Sulfhydryl Compounds; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D005978:Glutathione; D013974:Thyroxine