Review Article

Emerging Metabolic Targets in the Therapy of Hematological Malignancies

Figure 1

Glycolysis and molecular targets of glycolytic inhibitors. The solid arrows indicate glycolytic reactions. 2-Deoxyglucose (2-DG) inhibits hexokinase (HK), inducing early blockage of glycolytic pathway. 3-Bromopyruvate (3BrPA) inhibits HK and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), both blocking glycolytic flux. [3-dihydroxy-6-methyl-7-(phenylmethyl)-4-propylnaphthalene-1-carboxilic acid] (FX11) inhibits lactate dehydrogenase (LDH), further preventing the lactate production. Dichloroacetate (DCA) inhibits pyruvate dehydrogenase kinase (PDK), limiting the acetyl-CoA production by pyruvate dehydrogenase (PDH). GLUT1, glucose transport 1; HK, hexokinase; PGI, phosphoglucose isomerase; PFK, phosphofructokinase; TPI, triosephosphate isomerase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PGK, phosphoglycerate kinase; PGM, phosphoglycerate mutase; ENO1, enolase; PK, pyruvate kinase; LDH, lactate dehydrogenase; PDH: pyruvate dehydrogenase; PDK, pyruvate dehydrogenase kinase.
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