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# 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

- [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/)

## Related conditions

- [Lactic acidosis](https://durgical.com/en/conditions/lactic-acidosis/)
- [Hereditary paraganglioma and pheochromocytoma (SDH)](https://durgical.com/en/conditions/hereditary-paraganglioma-and-pheochromocytoma/)
- [Fumarase deficiency](https://durgical.com/en/conditions/fumarase-deficiency/)
- [Glioblastoma](https://durgical.com/en/conditions/glioblastoma/)

## Related

- [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/)
- [Glucose](https://durgical.com/en/biochemistry/molecules/glucose/)
- [Lactate](https://durgical.com/en/biochemistry/molecules/lactate/)
- [Pyruvate kinase](https://durgical.com/en/biochemistry/enzymes/pyruvate-kinase/)
- [Hexokinase](https://durgical.com/en/biochemistry/enzymes/hexokinase/)
- [Pentose phosphate pathway](https://durgical.com/en/biochemistry/pathways/pentose-phosphate-pathway/)
- [Isocitrate dehydrogenase](https://durgical.com/en/biochemistry/enzymes/isocitrate-dehydrogenase/)
- [Succinate dehydrogenase (complex II)](https://durgical.com/en/biochemistry/enzymes/succinate-dehydrogenase/)
- [Oncogenes and tumour suppressor genes](https://durgical.com/en/biochemistry/topics/oncogenes-and-tumour-suppressor-genes/)
- [NADPH](https://durgical.com/en/biochemistry/molecules/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [PKM: Pyruvate kinase PKM (human), UniProt P14618](https://www.uniprot.org/uniprotkb/P14618/entry) (UniProt, 2026); [Regulation of gene expression by Hypoxia-inducible Factor](https://reactome.org/PathwayBrowser/#/R-HSA-1234158) (Reactome, 2026); [TP53 Regulates Metabolic Genes](https://reactome.org/PathwayBrowser/#/R-HSA-5628897) (Reactome, 2026); [IDH1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/idh1/) (MedlinePlus, US National Library of Medicine, 2026); [FH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/fh/) (MedlinePlus, US National Library of Medicine, 2026); [VHL gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/vhl/) (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).

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