Tobin R B, Berdanier C D, Ecklund R E
J Environ Pathol Toxicol. 1979 Jul-Aug;2(6):1223-34.
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.
研究了L-甲状腺素（T4）处理对正常大鼠和T4处理大鼠肝脏代谢的影响。迅速切除肝脏并快速冷冻钳夹。测定了腺嘌呤核苷酸、糖酵解和三羧酸循环代谢物的水平。根据选定的底物浓度计算细胞质和线粒体中游离吡啶核苷酸的氧化还原比。T4处理导致较低的磷酸化状态，并使细胞质NAD和NADP的比率降低，线粒体NAD的比率降低。T4处理对NADP氧化还原状态的改变程度大于对NAD的改变，这意味着转氢酶反应失衡。糖酵解中间产物的变化很小，未显示出酶促变化的明显“交叉点”。T4引起的代谢物最显著变化为：柠檬酸增加、酮类增加和α-酮戊二酸减少。讨论了代谢物变化以及NAD和NADP氧化还原状态的代谢后果。T4处理未改变细胞质NAD磷酸化电位与氧化还原状态相关反应的平衡。细胞质和线粒体NAD的减少表明，T4对还原当量向线粒体转运的影响大于对氧化能力增强的影响。
