Influence of glycogen content on the effect of 2,4-dinitrophenol on the oxygen uptake by rat liver slices

Abstract When liver glycogen was reduced by fasting of the rats or by glyco-genolysis in vitro , 10 −4 M DNP had an inhibitory effect on basal oxygen consumption which was proportional to the glycogen content. With initial glycogen of 2 % or more, the rate of oxidation was enhanced. The action of variable doses of DNP (10 −5 to 0.5 × 10 −3 M ) depended also on tissue glycogen content. With low glycogen, only the inhibitory effect may be observed at all DNP levels. With high glycogen, DNP stimulated oxygen uptake; and with intermediate glycogen content, the effect of DNP was inhibitory or stimulating according to the dose employed. The inhibitory effect on respiration produced by DNP on slices with low glycogen content practically disappeared, or even a stimulating effect was observed, when fructose 1,6-diphosphate, pyruvate, citrate, α-ketoglutarate, succinate, malate, l (+)-glutamate, l (+)-aspartate, or l (+)-alanine were added. If glucose, fructose, acetate, butyrate, or hexanoate was added, the inhibitory effect was not reversed. Most of the substrates employed, in variable degree, increased oxygen uptake in the presence of DNP when the glycogen content was at a high level. The addition of ATP to the incubation medium ( ca . 0.005 M ) partially abolishes the inhibition produced on oxygen consumption by DNP in a low-glycogen liver, either with butyrate or without exogenous substrate.