Adenine nucleotide and lactate levels in organs from copper-deficient mice and brindled mice

Experiments were conducted with 12-d-old suckling male mice to investigate energy metabolism during copper deficiency. Brindled mice, which have a genetic defect that affects copper distribution, were compared to their normal brothers and to nonbrindled mice that were copper deficient (-Cu) because their dams were consuming a diet low in copper since impregnation and to a fourth group of control suckling mice (+Cu) from copper-supplemented dams. A second study was done with older mice. Dietary copper deficiency was initiated at birth through dams and continued for 7 wk. Organs were fast-frozen in liquid nitrogen and then analyzed for adenine nucleotides by high performance liquid chromatography and for lactate spectrophotometrically. Levels of ATP, ADP and AMP were equivalent for liver, brain, heart and kidney from the young mice regardless of their copper status. Nucleotide levels were low in spleens from brindled mice. Lactate concentrations were elevated in brains from both -Cu and brindled mice but not in other organs. Older -Cu mice, in comparison, did have lower ATP levels and "energy charge" in heart but not liver compared to +Cu mice. Lactate levels were not higher despite a much lower cytochrome c oxidase activity. Thus, organs from copper-deficient mice with major reductions in cytochrome c oxidase activity do not necessarily have altered steady-state levels of adenine nucleotides. The reduction in cytochrome c oxidase activity in copper deficiency may play a minor role in the expression of pathophysiology.