6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat brain.

The concentration of fructose 2,6-bisphosphate in the brain remained stable during starvation and early stages of ischaemia, but decreased in diabetes or after lengthened ischaemia. 6-Phosphofructo-1-kinase activity was also decreased in diabetic and ischaemic animals, whereas 6-phosphofructo-2-kinase was not modified. The concentration of the bisphosphorylated metabolite seems to be remarkably constant under a wide variety of experimental conditions, suggesting that it plays an essential role in the basal activation of 6-phosphofructo-1-kinase. Purified 6-phosphofructo-2-kinase also showed fructose-2,6-bisphosphatase activity with an activity ratio similar to that of the purified heart isoenzyme. The brain enzyme also has a net charge similar to that of the heart isoenzyme. Its activity is not modified by sn-glycerol 3-phosphate, and it is more sensitive to citrate than the liver or muscle isoenzyme. Moreover, the enzyme from brain, similarly to that from heart and muscle, is not modified by the cyclic AMP-dependent protein kinase or protein kinase C. A near-full-length cDNA probe from liver hybridized with RNA from brain and heart. In both cases, a major band of 6.8 kb of RNA and a minor one of 4 kb of RNA were detected. All these properties support the hypothesis that brain contains a different isoenzymic form from that of liver and muscle, and it is probably related to the heart isoform.