Warburg Effect

Curator(s): Peter D'Adamo

In oncology, the Warburg effect is the observation that most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, rather than by a comparatively low rate of glycolysis followed by oxidation of pyruvate in mitochondria like most normal cells. Lactate production is typically restricted to anaerobic conditions when oxygen levels are low, however, cancer cells preferentially channel glucose towards lactate production even when oxygen is plentiful, a process termed 'aerobic gycolysis' or the Warburg Effect. The latter process is aerobic (uses oxygen). Malignant rapidly-growing tumor cells typically have glycolytic rates that are up to 200 times higher than those of their normal tissues of origin; this occurs even if oxygen is plentiful.    

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Warburg Effect cluster_node48 !4 cluster_MITOCHONDRIA MITOCHONDRIA cluster_node49 !1 cluster_ER ER cluster_node50 !6 node1 17 Glucose Glucose->node1 Glucose GLUT transporters Glucose->GLUT transporters Glycolysis Glycolysis->Glucose node2 8 GLUT transporters->node2 GLUT transporters node4 GLUT transporters->node4 node3 3 node5 5 node6 c-Myc node6->GLUT transporters node6->node5 c-Myc lactate dehydrogenase A LDHA node6->LDHA node6->node4 node7 1 Ras Ras->GLUT transporters Ras->node7 Ras PFK Ras->PFK node16 MEK1/2 Ras->node16 Growth factors GFR Growth factors->GFR node8 10 GFR->node8 GFR PIK3 GFR->PIK3 node9 5 PIK3->node9 PIK3 AKT PIK3->AKT node10 29 AKT->GLUT transporters AKT->node10 AKT mechanistic target of rapamycin (serine/threonine kinase) MTOR AKT->MTOR AKT->PFK AKT->node4 AKT->node4 BCL2-associated X protein BAX AKT->BAX node11 16 AMPK AMPK->node11 AMPK AMPK->MTOR acetyl-CoA carboxylase alpha ACACA AMPK->ACACA node12 20 MTOR->node12 MTOR Protein synthesis MTOR->Protein synthesis Cell growth MTOR->Cell growth SREBP MTOR->SREBP hypoxia inducible factor 1,alpha subunit (basic helix-loop-helix transcription factor) HIF1A MTOR->HIF1A LKB1 LKB1->AMPK PFK->Ras node20 Fructose 1,6-bisphosphate PFK->node20 node13 Fructose 6-phosphate node13->PFK node14 node14->node13 node15 2 node16->node15 MEK1/2 node18 Erk1/2 node16->node18 node17 15 node18->node6 node18->node17 Erk1/2 Amino acids Amino acids->MTOR node19 10 HIF1A->node19 HIF1A pyruvate kinase,muscle PKM2 HIF1A->PKM2 Increased gene expression HIF1A->LDHA node21 Glyceraldehyde 3-P node20->node21 node21->node20 PEP node21->PEP PEP->PKM2 Pyruvate PKM2->Pyruvate node22 2 Pyruvate->node22 Pyruvate Pyruvate->LDHA node35 Pyruvate (2) Pyruvate->node35 node23 node23->Pyruvate NADP->NADPH Lactate LDHA->Lactate node25 1 Fatty acid oxidation Acetyl coenzyme A Fatty acid oxidation->Acetyl coenzyme A Fatty acids node27 Citrate (2) ATP citrate lyase ACLY node27->ACLY node28 10 p53 p53->node28 p53 node29 p53->node29 TIGAR p53->TIGAR node24 alpha-ketoglutarate node29->node24 Glutamine Glutamine->node29 node30 D-Glutamine and D -glutamate metabolism node30->Glutamine node31 6-Phosphonoglucono -D-lactone node32 6-P -gluconate node31->node32 TIGAR->node31 node33 Ribulose-5P node32->node33 NADP->NADPH Nucleotide sugar metabolism node33->Nucleotide sugar metabolism node34 Acetyl Co-A (2) ACLY->node34 node34->ACACA Fatty acid biosynthesis ACACA->Fatty acid biosynthesis node37 16 node38 1 node40 5 Apoptosis node43 2 node44 9 caspase 9,apoptosis-related cysteine peptidase CASP9 CASP9->node44 CASP9 caspase 3,apoptosis-related cysteine peptidase CASP3 CASP9->CASP3 node45 26 CASP3->node45 CASP3 caspase 7,apoptosis-related cysteine peptidase CASP7 CASP3->CASP7 node46 5 CASP7->Apoptosis CASP7->node46 CASP7 node47 1 SUMOylation SUMOylation->HIF1A SUMOylation->node47 SUMOylation node26 node26->node25 node26->Acetyl coenzyme A node4->node3 Glucose 6 phosphate node4->Glucose 6 phosphate node39 VDAC/ANT node4->node39 Glucose 6 phosphate->node14 Glucose 6 phosphate->node31 NADP->NADPH node39->node38 VDAC/ANT inositol 1,4,5-trisphosphate receptor,type 1 ITPR1 node39->ITPR1 Mitochondrial membrane instability node39->Mitochondrial membrane instability node36 node36->node26 Succinate node24->Succinate BAX->node37 BAX BAX->node39 cytochrome c,somatic CYCS CYCS->node43 CYCS Cytochrome C release CYCS->Cytochrome C release Cytochrome C release->CASP9 node42 Ca2+ node42->CYCS Citrate Citrate->node24 uncoupling protein 2 (mitochondrial,proton carrier) UCP2 Citrate->UCP2 UCP2->node27 Fumarate Malate Fumarate->Malate Malate->node23 Oxaloacetate Malate->Oxaloacetate ITPR1->node42 Oxaloacetate->Citrate node41 NADH-ubiquinone reductase (Complex I) node41->node40 NADH-ubiquinone reductase (Complex I) node35->node26 Succinate->Fumarate Succinate->node41 print "