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ORIGINAL RESEARCH ARTICLE

Fructose-2,6-Bisphosphate Is Lower in Copper Deficient Rat Cerebellum Despite Higher Content of Phosphorylated AMP-Activated Protein Kinase

Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, Duluth, Minnesota 55812

To whom requests for reprints should be addressed at ¹ Department of Biochemistry and Molecular Biology, University of Minnesota Medical School Duluth, 1035 University Drive, Duluth, MN 55812. E-mail: jprohask{at}d.umn.edu

Limitation in copper (Cu) leads to pathophysiology in developing brain. Cu deficiency impairs brain mitochondria and results in high brain lactate suggesting augmented anaerobic glycolysis. AMP activated protein kinase (AMPK) is a cellular energy "master-switch" that is thought to augment glycolysis through phosphorylation and activation phosphofructokinase 2 (PFK2) resulting in increases of the glycolytic stimulator fructose-2,6-bisphosphate (F2,6BP). Previously, Cu deficiency has been shown to augment cerebellar AMPK activation. Cerebella of Cu-adequate (Cu+) and Cu-deficient (Cu–) rat pups were assessed to evaluate if AMPK activation in Cu– cerebella functioned to enhance PFK2 activation and increase F2,BP concentration. Higher levels of pAMPK were detected in Cu– cerebella. However, PFK2 activity, mRNA, and protein abundance were not affected by Cu deficiency. Surprisingly, F2,6BP levels were markedly lower in Cu– cerebella. Lower F2,6BP may be due to inhibition of PFK2 by citrate, as citrate concentration was significantly higher in Cu– cerebella. Data suggest AMPK activation in Cu– cerebellum does not augment glycolysis through a PFK2 mechanism. Furthermore, other metabolite data suggest that glycolysis may actually be blunted, since levels of glucose and glucose-6-phosphate were higher in Cu– cerebella than controls.

Key Words: copper-deficient • rat, cerebellum • fructose-2,6-bisphosphate • AMPK • citrate