Biochemistry · Topic
Warburg effect (aerobic glycolysis in cancer) !
Many tumour cells burn glucose and make lactate even with oxygen present; this gives them building blocks to grow fast.
Updated 2026-11-01
Key facts
- Aerobic glycolysis: the tumour cell turns much of its glucose into lactate even with O₂ and working mitochondria.
- It yields little ATP per glucose, but it is fast and diverts intermediates to nucleotides (pentose pathway), amino acids and lipids.
- Oncogenes and suppressors drive it: HIF-1α, MYC, RAS and the PI3K–AKT pathway raise GLUT1, hexokinase 2 and LDH-A; p53 restrains it.
- The PKM2 isoform of pyruvate kinase, with low activity, accumulates glycolytic intermediates for biosynthesis.
- The basis of ¹⁸F-fluorodeoxyglucose PET: tumours take up a lot of glucose.
In detail
- Oncogenic signalling increases glucose entry (GLUT1) and phosphorylation (hexokinase 2).
- Glucose 6-phosphate feeds the pentose pathway: ribose for DNA and NADPH for lipids and glutathione.
- Intermediates such as 3-phosphoglycerate yield serine and glycine; slow PKM2 helps them pile up.
- Pyruvate is reduced to lactate (LDH-A), which regenerates NAD⁺ to keep glycolysis going; lactate leaves through MCT4.
- Lactate acidifies the surroundings, favours invasion and dampens lymphocytes.
- Some hereditary tumours show it clearly: SDH, fumarase or VHL mutations stabilise HIF («pseudohypoxia»); mutant IDH makes the oncometabolite 2-hydroxyglutarate.
Clinical notes
- FDG PET-CT locates tumours and metastases by their high glucose uptake (inflammation also lights up).
- Large or haematological cancers can cause type B lactic acidosis.
- Gliomas and leukaemias with mutant IDH1/2: 2-hydroxyglutarate disrupts methylation; mutant-IDH inhibitors exist.
- SDH paraganglioma and fumarase-related leiomyomatosis with kidney cancer are examples of Krebs cycle enzymes acting as suppressors.
Pathways
Related conditions
Related
- Glycolysis
- Glucose
- Lactate
- Pyruvate kinase
- Hexokinase
- Pentose phosphate pathway
- Isocitrate dehydrogenase
- Succinate dehydrogenase (complex II)
- Oncogenes and tumour suppressor genes
- NADPH
Test yourself
Think of the answer, then tap the question to see it.
What is Warburg aerobic glycolysis?
The conversion of glucose to lactate by tumour cells even when oxygen is available.
If it yields less ATP, what does the tumour cell gain from the Warburg effect?
Speed and building blocks: intermediates for nucleotides, amino acids and lipids, and NADPH from the pentose pathway.
Which imaging test exploits the Warburg effect?
PET with ¹⁸F-fluorodeoxyglucose, which accumulates in cells that take up a lot of glucose.
Which oncometabolite does mutant IDH make?
2-hydroxyglutarate, which inhibits α-ketoglutarate-dependent enzymes and disrupts DNA methylation.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: PKM: Pyruvate kinase PKM (human), UniProt P14618 (UniProt, 2026); Regulation of gene expression by Hypoxia-inducible Factor (Reactome, 2026); TP53 Regulates Metabolic Genes (Reactome, 2026); IDH1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); FH gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); VHL gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.