Bisphosphoglyceratemutase (BPGM): a central role in metabolism of proliferating cells.

Many kind of cancer cells exploit glycolysis rather than oxidative phosphorylation for energy production even in the presence of oxygen. This kind of metabolism, although less efficient in terms of ATP production, generates high levels of glycolytic intermediates necessary to support the high biosynthetic flux of rapidly proliferating cells. . This mechanism is further enhanced in cancer cells by the expression of a particular form of pyruvate kinase -M2 (PKM2) which promote a low efficiency glycolysis (in terms or ATP production) and consequently an increase in the formation of biosynthetic metabolites. In this work we investigate the role of Bisphosphogliceratemutase (BPGM) an enzyme involved in the metabolic reprogramming of highly proliferating cancer cells. BPGM acts both as a mutase, converting the glycolytic intermediate 1,3-bisphosphoglycerate to 2,3-bisphosphoglycerate and as a phosphatase, converting the 1,3-bisphosphoglycerate to 3-phosphoglycerate. BPGM is an erythrocyte-specific enzyme but our real time PCR and western blotting experiments show its expression in many cancer cell lines and in proliferating primary human fibroblasts. BPGM silencing lead to a strong decrease of cell proliferation rate BPGM activity in cancer cell lead to the skipping of the first ATP production in the glycolytic pathway of glycolysis, causing an increase of glycolytic flux necessary to sustain the high rate of intermediates production needed for support cancer cells growth.