The effect of cobalt ions on energy metabolism in the rat.

Abstract

Cobalt treatment for 8 days significantly depressed respiration of isolated rat heart mitochondria when citrate or α-ketoglutarate but not succinate was utilized as added substrate. The depressed respiration of the cardiac mitochondria in citrate media was accompanied by an increased accumulation of α-ketoglutarate in the incubation media. Cobalt treatment also reduced the ferricyanide-linked ketoglutarate dehydrogenase activity of isolated rat heart mitochondria. For the first 3 days, isolated diaphragm segments from cobalt-treated rats utilized glucose and pyruvate at rates higher than the controls but respired at reduced rates if ketoglutarate or octanoate was used as the substrate. After 4 days of cobalt-treatment, oxygen uptake was consistently lower in diaphragm segments for all four substrates and remained so for the next 3 days of treatment. By contrast, heart slices from cobalt-treated rats had a consistently lower oxygen uptake for glucose, pyruvate, α-ketoglutarate, and octanoate, commencing with the first day of cobalt injection and continuing for the next 7 days. Significant differences were found in resting glycogen (decreased), glucose uptake (increased), and glycogen deposition (decreased) in isolated diaphragm taken from cobalt-treated rats. Cobalt treatment had no effect on blood pyruvate and lactate levels.