ISOZYMIC COMPOSITION AND REGULATORY PROPERTIES OF PHOSPHOFRUCTOKINASE FROM WELL-DIFFERENTIATED AND ANAPLASTIC MEDULLARY-THYROID CARCINOMAS OF THE RAT

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 135-142
Abstract
Acceleration of glycolysis is, in general, a characteristic of neoplasia. Previous studies have shown that this increases in glycolysis is achieved by quantitative increases in the activities of the key regulatory enzymes, hexokinase, phosphofructokinase (PFK) and/or pyruvate kinase, which are often accompanied by isozymic alterations that facilitate glycolysis. The alterations in the activity, isozymic profile and kinetic-regulatory properties of PFK from the medullary thyroid carcinomas of the rat, which represent a model for the neuroectodermally derived tumors in humans, was investigated. Undifferentiated tumors showed a decrease in the enzyme activity as compared to the highly differentiated tumors. This decrease in PKF activity was accompanied by an increase in the expression of the liver-type isozyme of PFK. The enzymes from the 2 tumor types showed no significant differences in their affinity and cooperativity towards the substrates, fructose 6-phosphate and ATP. The tumor PFK showed major differences with respect to their behavior toward the allosteric regulators of the enzymes, ATP, citrate and fructose 2,6-diphosphate; the latter is a recently discovered activator of the enzyme. The enzyme from the undifferentiated tumor was less sensitive to citrate inhibition, which was more readily reversed by cAMP. In addition, it was less sensitive to ATP inhibition at low fructose 6-phosphate concentrations. More importantly, the enzyme from the undifferentiated tumors was more sensitive to the activation by fructose 2,6-diphosphate especially when inhibited by citrate and ATP. The altered regulatory properties of the enzyme from the undifferentiated tumors most probably reflect its altered isozymic composition, i.e., increaese in the liver-type isozyme. The preferential expression of the liver-type isozyme by undifferentiated and rapidly replicating cancer cells may be explained in terms of the unique regulatory properties of this isozyme. Although the concentrations of fructose 2,6-diphosphate were comparable in these 2 tumor types, the higher sensitivity of the liver-type PFK to activation by this compound may permit accelerated glycolytic flux observed in undifferentiated tumors, despite a decrease in total PFK activity.

This publication has 25 references indexed in Scilit: