In this study, we investigated the alterations in the activity, subunit profile, and kinetic regulatory properties of phosphofructokinase (PFK) from human gliomas compared with those from normal human brain. Gliomas showed a decrease in the enzyme activity as compared to normal brain. This decrease in PFK activity was accompanied by a relative increase in the expression of the liver type subunit of PFK. The enzymes from the tumor and normal brain showed no significant differences in their affinity toward the substrate fructose 6-phosphate. However, tumor and normal brain PFK showed major differences with respect to their behavior towards citrate and fructose 2,6-bisphosphate. The enzyme from the gliomas was less sensitive to citrate inhibition. More importantly, the enzyme from the tumor was more sensitive to the activation by fructose 2,6-bisphosphate. In addition, we found that in gliomas the L-type subunit could be phosphorylated, most probably by a cyclic AMP-independent protein kinase. This phosphorylation could not be detected in normal human brain. It is proposed that the preferential expression of the liver type subunit by undifferentiated cancer cells may be explained in terms of the unique regulatory properties of this isozyme.

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