Carbohydrate in Contrast to Protein Feeding Increases the Hepatic Content of Active Thyroxine-5′-Deiodinase in the Rat*

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Abstract
Dietary constituents have specific effects on serum T3 and rT3 concentrations. We have previously demonstrated that glucose- compared to protein-fed rats have higher serum T3 levels. These alterations reflected greater hepatic T4- 5′-deiodinase activity in the glucose-fed group. To determine whether the greater enzyme activity was consequent to an increase in the hepatic content of active enzyme or sulfhydryl cofactor, further studies on T4-deiodination have been performed in liver homogenate preparations from glucose (20% glucose in water) and Purina (25% protein)-fed rats compared to 72-h fasted rats treated with L-T4. The Purina-fed animals demonstrated greater (P < 0.01) T4- 5′-deiodinase activity (T4 to T3) than the 72-h fasted group. However, hepatic T4-5-deiodinase activity (T4 to rT3) was similar for these dietary groups. Homogenate enrichment with the thiol reagent dithioerythritol (DTE) reversed the difference noted between the Purina-fed and the fasted group. Moreover, the hepatic content of nonprotein sulfhydryls and reduced glutathione was significantly less (P < 0.005) in the fasted than in the Purina-fed group. In addition, the Vmax values for hepatic T4-5′-deiodinase (DTE-enriched homogenate) were almost identical in the Purina-fed and fasted groups at 2.1 ± 0.05 and 2.0 ± 0.02 T3 pmol/min · mg protein, respectively, and the Km values were similar at 2.5 μM and 2.6 μM, respectively. Thus, protein feeding reversed the effect of fasting by increasing the availability of enzyme cofactor. Glucose-fed animals possessed greater (P < 0.01) T4-5′-deiodinase and T4-5-deiodinase activity than did the Purina-fed group. Homogenate enrichment with DTE did not obliterate the differences noted. Moreover, the hepatic content of nonprotein sulfhydryls and reduced glutathione was less (P < 0.005) in the glucose- than in the Purina-fed group. In addition, hepatic preparations from a 15% glucose-fed group demonstrated greater (P < 0.001) T4-5′-deiodinase activity than a 5% glucose-fed group and a Purina-fed group, despite no difference in the hepatic content of sulfhydryl compounds among the various groups. Thus, the glucose effects on hepatic T4-5′-deiodinase were mediated independently of the liver sulfhydryl content. T4-5′-deiodinase kinetic studies elucidated the probable mechanism of the glucose effect. The enzyme Km for T4 was similar for both the glucose-fed and Purina-fed groups at 2.4 μM and 2.5 μM, respectively. However, the Vmax was significantly greater (P < 0.001) in the glucose-fed group at 3.4 ± 0.01 T3 pmol/min-mg protein compared to that in the Purina group at 2.5 ± 0.05 T3 pmol/min mg protein. Thus, glucose feeding induces an increase in the hepatic content of active enzyme. The specific effects of the various diets are further illustrated by the alterations in the serum iodothyronine values. Serum T3 was significantly higher (P < 0.005) in the glucose-fed (49 ± 3 ng/100 ml) than in the Purina-fed group (31 ± 3 ng/100 ml). Serum rT3 was significantly higher (P < 0.005) in the fasted group (36 ± 3 ng/100 ml) compared to the Purina-fed group (15 ± 1 ng/100 ml). Thus, dietary constituents, which enhance hepatic T4-5′- deiodinase activity, mediate their effects through different but specific mechanisms. Protein feeding increases the sulfhydryl cofactor, whereas glucose feeding increases the hepatic content of active enzyme.

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