Fig. 2. Inhibitors of glucose metabolism.

Glucose is taken up into the cell by glucose transporters (GLUT) and phosphorylated by hexokinases HK1 and HK2. Glucose 6-phosphate (P) and its downstream intermediates can either be converted to pyruvate or fuel biosynthesis through the hexosamine biosynthesis pathway, the pentose phosphate pathway (PPP), via glycerol 3-P production or via serine biosynthesis pathways. Hexosamine has a key role in glycosylation. The PPP provides ribose 5-P for nucleotide synthesis and NADPH. Glycerol 3-P provides the backbone for lipid synthesis. Serine biosynthesis has a key part in amino acid metabolism and nucleotide metabolism through control of one-carbon (1C) metabolism (see Fig. 5). Pyruvate can either enter the tricarboxylic acid (TCA) cycle as acetyl-CoA through the mitochondrial pyruvate carrier (MPC) and pyruvate dehydrogenase, be converted to lactate by lactate dehydrogenase (LDH) and exported through the monocarboxylate transporter (MCT) or be converted to alanine via glutamic–pyruvic transaminase (GPT). Inhibitors (blue) and activators (purple) of key enzymes (red) or transporters (white) are shown. In addition to producing energy by contributing reducing equivalents to the electron transport chain, the TCA cycle is an important source of aspartate for nucleotide metabolism (see Fig. 5). The conversion of pyruvate to lactate has a key role in maintaining cellular NAD⁺ to NADH ratios. aKG, α-ketoglutarate; OAA, oxaloacetate; PDH, pyruvate dehydrogenase; PHGDH, phosphoglycerate dehydrogenase; PKM2, pyruvate kinase muscle isozyme 2; SHMT, serine hydroxymethyl transferase.