Metabolism of intact reticulocytes and mitochondria under lowered energy load induced by cycloheximide

Cycloheximide was used to decrease the energy load by inhibitors of hemoglobin synthesis as the major ATP-consumer in intact rabbit reticulocytes. Inhibitor concentrations up to 2.5 X 10(-5) M led to decreased ATP-production at simultaneously elevated ATP/ADP ratios. Higher inhibitor levels resulted in further decreasing ATP-production but now in the reverse parallel to declining ATP/ADP ratios. Studies with intact reticulocyte mitochondria revealed almost no influence on respiration rates at the low range of concentrations but increasing inhibitions of state 3, state 4 and uncoupled respiration as well, with a 50% inhibition around 3 mM. Thus the dual action of the inhibitor is obviously due to the specific suppression of protein synthesis on the one hand and the unspecific inhibition of mitochondrial respiration on the other. Similar conclusions have been drawn by using ouabain to suppress the ATP-consumption by Na-K-ATPase. A preliminary load characteristic for rabbit reticulocytes with glucose as substrate is presented.