The levels of
fructose 2,6-bisphosphate and
glucose 1,6-bisphosphate and the activities of the key glycolytic
enzymes have been studied in T- and B-lymphocytes, and in B-
chronic lymphocytic leukemia cells (B-CLL). In both kinds of cells these two bisphosphorylated metabolites have been identified and are present at similar concentrations. Their
phosphofructokinase, like that of other normal or tumoral cells, is sensitive to these activators.
Fructose 2,6-bisphosphate is the most potent stimulator; it displays the properties of a positive effector. It greatly increases the affinity for
fructose 6-phosphate and relieves the inhibition by
adenosine triphosphate, without changing Vmax. This effect is also synergistic with
adenosine monophosphate. Despite few differences in the activity of
phosphofructokinase and in the content of its main effectors in B-lymphocytes and in B-CLL cells, the kinetic properties of the
enzyme from B-CLL cells were different, the
enzyme being more sensitive to
fructose 2,6-bisphosphate (Ka 2 orders of magnitude lower) and to
glucose 1,6-bisphosphate than the
enzyme from normal lymphocytes. The results reported showing that
phosphofructokinase from B-CLL lymphocytes is altered in regulatory properties and the observed changes, in comparison to
phosphofructokinase from normal B-lymphocytes, fit well with the hypothesis that
fructose 2,6-bisphosphate can also assume a regulatory role in these
cancer cells characterized by proliferation and accumulation of relatively mature-appearing lymphocytes.