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Control of Phosphofructokinase by Fructose 2,6-Bisphosphate in B-Lymphocytes and B-Chronic Lymphocytic Leukemia Cells¹

Department de Bioquimica, Facultat de Medicina, Universitat de Barcelona [D. C., R. B.], and Laboratori d'Hematologia, Servei d'Hematologia Biologica i Escola Professional d'Hematologia "Farreras Valenti," Hospital Clinic i Provincial de Barcelona [D. C., J. L. V-C., A. P.], Barcelona, Spain

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 V_max. 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 (K_a 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.

¹ This work has been supported by a Grant from "Fondo de Investigaciones Sanitarias de la Seguridad Social."

² To whom requests for reprints should be addressed, at Departament de Bioquímica, Facultat de Medicina, Universitat de Barcelona, Zona Universitária Pedralbes, 08028 Barcelona, Spain.

Received 7/28/86. Revised 11/26/86. Accepted 1/ 2/87.

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