Effect of L-thyroxine treatment on the levels of various hepatic metabolites in rats.

The effects of L-thyroxine (T4) treatment upon hepatic metabolism of control and T4 treated rats was studied. Livers were excised and freeze-clamped rapidly. The levels of adenine nucleotides and glycolytic and TCA cycle metabolites were determined. The redox ratios of free pyridine nucleotides of cytoplasm and mitochondria were calculated from selected substrate concentrations. T4 treatment resulted in lower phosphorylation states and caused reduction in ratios of cytoplasmic NAD and NADP and reduction in the ratio of mitochondrial NAD. T4 treatment changed the redox state of NADP to a greater degree than that of NAD, implying disequilibrium of the transhydrogenase reaction. Changes in glycolytic intermediates were minimal and did not indicate significant "crossover points" of enzymatic change. The most striking changes in metabolites caused by T4 were: increase in citrate, increase in ketones, and decrease in alpha-ketoglutarate. The metabolic consequences of changes in metabolites and of redox states of NAD and NADP were discussed. The equilibrium of reactions interrelating the phosphorylation potential and redox state of cytoplasmic NAD was not altered by T4 treatment. Reduction of cytoplasmic and mitochondrial NAD suggests a greater effect of T4 upon the transport of reducing equivalents into mitochondria than upon enhancement of oxidative capacity.