# Biochemistry of Cancer Metabolism > Warburg effect, glutaminolysis, oncometabolites and FDG-PET logic of tumour metabolism for MBBS Biochemistry preparation. - Canonical URL: https://prepelephant.com/topics/mbbs/biochemistry/biochemistry-of-cancer-metabolism - Exam / course: MBBS · Subject: Biochemistry - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-02 - Last updated: 2026-10-02 - How to cite: "Biochemistry of Cancer Metabolism", PrepElephant, https://prepelephant.com/topics/mbbs/biochemistry/biochemistry-of-cancer-metabolism ## Direct answer Rewiring metabolism is a hallmark of cancer, not a by-product of it. Most tumours ferment glucose to lactate even when oxygen is plentiful — the Warburg effect — trading ATP yield for speed, NADPH and biosynthetic intermediates, which is exactly why FDG-PET lights them up. Beyond glucose, many cancers become addicted to glutamine, feeding glutaminolysis into the citric acid cycle for carbon, nitrogen and redox balance; they ramp up lipogenesis and the pentose phosphate pathway for membrane and nucleotide synthesis; and some carry IDH1/2 mutations that create a genuinely new oncometabolite, 2-hydroxyglutarate, which rewires epigenetics. Growth-factor and oxygen sensing (HIF-1α, PI3K-AKT-mTOR) sits upstream of every one of these switches, so oncogenic signalling and metabolic reprogramming are two descriptions of one process. ## What you must remember - **Warburg effect:** aerobic glycolysis — high glucose uptake with lactate export through monocarboxylate transporters despite normoxia; two ATP per glucose, but rapid, and coupled to macromolecule synthesis; Otto Warburg described it in the 1920s. - **FDG-PET logic:** fluorodeoxyglucose is phosphorylated by hexokinase and then trapped — it cannot leave through GLUT transporters or proceed down glycolysis — so radioactivity accumulates in proportion to glycolytic flux; standard in lymphoma staging in Indian practice. - **HIF-1α:** stabilised when prolyl hydroxylation fails in hypoxia; induces GLUT1, glycolytic enzymes and VEGF — the molecular link between hypoxia, glycolysis and angiogenesis. - **Glutaminolysis:** glutaminase converts glutamine to glutamate, then α-ketoglutarate; glutamine also supplies amide nitrogen for nucleotides and NADPH through malic enzyme — the basis of glutamine addiction. Asparaginase starves lymphoblasts of asparagine in acute lymphoblastic leukaemia protocols, a metabolic drug disguised as chemotherapy. - **Oncometabolite:** mutant IDH1/2 produces D-2-hydroxyglutarate, which inhibits TET2 and histone demethylases, producing the glioma CpG-island methylator phenotype; ivosidenib (IDH1) and enasidenib (IDH2) block this in AML. - **Biosynthetic diversion:** tumours express the embryonic PKM2 isoform of pyruvate kinase; glucose carbon flows to serine and glycine (one-carbon pool), ribose (pentose phosphate pathway) and exported citrate for fatty acid synthesis. - **Metformin:** activates AMPK and inhibits complex I; observational data suggest outcome benefit in diabetics with cancer, but it is a signal, not proven therapy — quote it that way. ## Numbers worth knowing: reading a tumour's metabolic budget A 62-year-old smoker undergoes FDG-PET for a lung mass and the mediastinal nodes glow. The chemistry underneath: the tumour overexpresses GLUT1 and hexokinase-2, so FDG floods in, is phosphorylated to FDG-6-phosphate, and is stuck — no glucose-6-phosphatase to release it, no glycolytic step to consume it. Radioactivity therefore accumulates exactly in proportion to the Warburg flux, and the reporter's standardised uptake value is, in effect, a glycolytic rate measurement. Move to a different patient, a young man with a frontal glioma: magnetic resonance spectroscopy shows a 2-hydroxyglutarate peak that did not exist in human biochemistry before the IDH mutation arose, and IDH inhibitors switch it off, letting blasts differentiate. Return to the ward where a child with acute lymphoblasts leukaemia receives asparaginase: her blasts cannot make enough asparagine, so depleting the plasma supply halts their protein synthesis. Three beds, one lesson — the metabolism is visible, measurable and druggable. ## Where students slip The classic error is equating the Warburg effect with hypoxia: oxygen availability is normal; the point is oxygen-independent glycolysis, and mitochondria remain functional and necessary for citrate, α-ketoglutarate and apoptotic signalling. The second error treats lactate as waste, when it is an exported fuel for oxidative cancer cells and stromal neighbours, shuttled much like the Cori cycle. A reliable viva question asks why mitochondria do not disappear from cancer cells: citric acid cycle intermediates are continuously drawn off for biosynthesis and must be replenished anaplerotically — glutamine and pyruvate carboxylase do that replenishing. ## Frequently asked questions ### Why do tumours prefer glycolysis despite its low ATP yield? Glycolysis is rapid, and its intermediates feed the pentose phosphate pathway, serine biosynthesis and lipogenesis — proliferation needs carbon skeletons and NADPH more than maximal ATP. ### What is an oncometabolite? A metabolite made only by a mutant enzyme, such as D-2-hydroxyglutarate from mutant IDH1/2, which alters epigenetics by inhibiting demethylases. ### Why is FDG trapped inside tumour cells? Hexokinase phosphorylates FDG to FDG-6-phosphate, which can neither exit through GLUT transporters nor continue down glycolysis, so the tracer accumulates with glycolytic flux. ### How does asparaginase kill lymphoblasts? Lymphoblasts lack adequate asparagine synthetase, so depleting extracellular asparagine halts their protein synthesis. ### Do all cancers show the Warburg effect? Most show heightened glycolysis, but oxidative phosphorylation persists and even dominates in some tumours — metabolism varies with tumour type and microenvironment.