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. 2013 Sep 3;123(9):3685–3692. doi: 10.1172/JCI69741

Figure 1. Aerobic glycolysis and glutaminolysis in cancer cells.

Figure 1

Oncoproteins drive the expression of genes involved in glycolysis and glutaminolysis, which results in production of excess amounts of lactate. Aberrant PI3K/AKT signaling and the transcriptional oncoproteins HIF-1α and MYC regulate the transcription of GLUT, HK2, TPI, ENO, and LDHA. HIF-1α induces the transcription of PFKFB3, which favors the production of F2,6BP, an allosteric activator of PFK1. The tumor suppressor protein p53 induces the expression of TIGAR, which dephosphorylates F2,6BP, blocking activation of PFK1 and inhibiting glycolysis. HIF-1α and MYC regulate the expression and splicing of the PKM2 isoform. MYC also regulates the expression of the glutamine transporter ASCT2 and GLS. Monocarboxylic acid transporters (MCTs) export lactate and protons and are regulated by HIF-1α and MYC. AcCoA, acetyl-CoA; ASP, aspartate; ASCT2, glutamine transporter; G, glucose; G6P, glucose-6-phosphate, F6P, fructose-6-phosphate; DHAP, dihydroxyacetone phosphate; GA3P, glyceraldehyde-3-phosphate; 1,3BPG, 1,3-bisphosphoglycerate; 2PG, 2-phosphoglycerate; 3PG, 3-phosphoglycerate; PEP, phosphoenolpyruvate; MDH, malate dehydrogenase; GOT, glutamic-oxaloacetic transaminase; GLUD1, glutamate dehydrogenase.