Regulation of cellular respiration by thyroid hormone. Spectroscopic evidence of mitochondrial control in intact rat liver

Abstract

In order to elucidate the role of the mitochondrial control (coupling) mechanism in the regulation of respiration in intact liver, we investigated perfused rat livers using direct spectrophotometry. The acute effects of fructose on hepatic concentrations of adenine nucleotides, inorganic phosphate, and citrate were also studied. In hypothyroid rat livers fructose caused a small stimulation of respiration, followed by marked inhibition lasting about 10 min. During the respiratory inhibition the redox state of the flavoproteins was reduced but that of cytochrome b was markedly oxidized. In euthyroid rats fructose first stimulated hepatic oxygen consumption, but the subsequent inhibition of respiration was much smaller than that in hypothyroid rats. During the inhibitory phase flavoproteins were reduced, but the oxidation of cytochrome b was significantly less than in hypothyroid rats. In hyperthyroid rat liver, fructose stimulated respiration without any subsequent inhibition. Flavoproteins and all cytochromes were reduced, and no transient oxidation was observed in contrast to hypo- and euthyroid rats. In all groups of rats fructose induced a prompt decrease in hepatic concentrations of ATP and inorganic phosphate. Fructose did not induce any acute changes in the concentrations of citrate, but in hyperthyroid rat liver the citrate concentration was three times greater than in hypo- or euthryoid liver. These results suggest that, in intact tissue also, mitochondrial control is important in the regulation of energy metabolism during the metabolism of fructose. Thyroxine treatment seems to loosen this coupling, perhaps by increasing the concentration and oxidation of fatty acids in the liver.