Skip to main content
WoMWeb of Medicine
SearchGraphHistory
Internal Medicine›Condition·Updated Jul 11, 2026·v1

Glycolysis

Glycolysis is the central metabolic pathway converting glucose to pyruvate with a net ATP yield of 2 per glucose. It provides biosynthetic precursors, redox equivalents, and signaling intermediates via lactate. Inborn errors (pyruvate kinase deficiency, G6PD deficiency, citrin deficiency, PGM1-CDG) are treatable with specific dietary interventions (MCT, d-galactose). The Warburg effect in cancer is both a diagnostic target and therapeutic vulnerability. Lactic acidosis is a strain biomarker; the lactate-to-pyruvate ratio guides etiology. Understanding glycolysis is essential for internal medicine, hematology, oncology, and metabolic disease management.

Moderate Evidence99 references·1,684 words·7 min read·v1
glycolysismetabolic pathwayWarburg effectlactic acidosisinborn errors of metabolismpyruvate kinase deficiencyG6PD deficiencycitrin deficiency

Quick Reference

RxDrug of choiced-Galactose for PGM1-CDG; MCT oil for citrin deficiency
AltAlternativesSodium pyruvate, ursodeoxycholic acid, nitrogen scavengers for citrin deficiency; arginine for aldolase A deficiency (investigational)
⊘AvoidIntravenous fructose in citrin deficiency; oxidant drugs (sulfonamides, dapsone, nitrofurantoin) in G6PD deficiency
DxTest of choiceLactate and pyruvate levels with calculated lactate-to-pyruvate ratio; G6PD activity assay; plasma amino acids (citrulline) for citrin deficiency
ScKey scoreLactate-to-pyruvate ratio (normal ~10-20): >25 suggests mitochondrial dysfunction; <10 suggests increased glycolysis
→When to referRefer to clinical geneticist or metabolic specialist for suspicion of inborn error of glycolysis; to hematologist for unexplained hemolytic anemia; to oncologist for Warburg-related therapeutic decisions
Glycolysis is not just an anaerobic ATP source but a hub for biosynthetic intermediates, redox balance, and signaling. Recognize inborn errors as treatable causes of hemolytic anemia, rhabdomyolysis, and neonatal cholestasis. The Warburg effect is both a diagnostic target (FDG-PET) and therapeutic opportunity.
Glycolysis is the central catabolic pathway converting glucose to pyruvate with net 2 ATP and 2 NADH per molecule. It operates in all cells, is the sole energy source in [[erythrocyte]]s, and integrates with biosynthesis, redox balance, and signaling. Disruptions cause hemolytic anemia, rhabdomyolysis, and cancer (Warburg effect). Therapeutic targeting includes PFKFB3, LDHA, and MCT inhibitors.

Overview and Recommendations

Key Facts

  • •Glycolysis is a ten-step cytosolic pathway that converts one glucose (6C) into two pyruvate (3C), producing a net of 2 ATP and 2 NADH per glucose. It is the only energy-yielding pathway in erythrocytes, which lack mitochondria.
  • •The pathway is organized into an energy-investment phase (steps 1-5, consuming 2 ATP) and an energy-payoff phase (steps 6-10, generating 4 ATP). Three irreversible steps, hexokinase/glucokinase, PFK-1, and pyruvate kinase, are the primary regulatory nodes.
  • •PFK-1 is the rate-limiting enzyme, activated by fructose-2,6-bisphosphate and AMP, inhibited by ATP and citrate. The bifunctional enzyme PFKFB2 synthesizes and degrades fructose-2,6-bisphosphate, integrating hormonal signals from insulin and glucagon.
  • •Lactate, long dismissed as waste, is a major circulating fuel, gluconeogenic precursor, and signaling molecule via lysine lactylation. The lactate-to-pyruvate ratio helps distinguish causes of lactic acidosis: >25 suggests impaired mitochondrial oxidation, <10 favors increased glycolytic flux.
  • •Inborn errors of glycolysis include pyruvate kinase deficiency (chronic hemolytic anemia), G6PD deficiency (hemolytic anemia after oxidative stress), and citrin deficiency (neonatal cholestasis, hyperammonemia). PGM1-CDG is treatable with d-galactose.

Mechanism Summary

  • •Glucose enters cells via GLUT transporters and is phosphorylated by hexokinase (low Km, inhibited by G6P) or glucokinase (high Km, no product inhibition) to glucose-6-phosphate, committing it to the pathway.
  • •Glucose-6-phosphate is isomerized to fructose-6-phosphate by phosphoglucose isomerase (GPI). PFK-1 then phosphorylates F6P to fructose-1,6-bisphosphate (F1,6BP) in the first committed, irreversible step.
  • •Aldolase cleaves F1,6BP into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). Triosephosphate isomerase (TPI) interconverts DHAP and G3P, a catalytically perfect enzyme that also generates the toxic byproduct methylglyoxal.
  • •GAPDH oxidizes G3P to 1,3-bisphosphoglycerate while reducing NAD+ to NADH. This step requires NAD+; the NADH must be reoxidized to sustain flux, via the malate-aspartate shuttle (aerobic) or lactate dehydrogenase (anaerobic).
  • •Phosphoglycerate kinase (PGK) performs substrate-level phosphorylation, transferring phosphate from 1,3-BPG to ADP, producing 3-phosphoglycerate and the first ATP (2 per glucose).
  • •Phosphoglycerate mutase (PGM) converts 3-PG to 2-phosphoglycerate via a 2,3-BPG intermediate. Enolase dehydrates 2-PG to phosphoenolpyruvate (PEP), a high-energy enol phosphate.
  • •Pyruvate kinase (PK) transfers phosphate from PEP to ADP, generating pyruvate and the second ATP (2 per glucose). PK is allosterically activated by F1,6BP (feed-forward) and inhibited by ATP and alanine. Four PK isoforms exist; PKM2 in cancer cells can switch between active tetramer and less active dimer.
  • •Under aerobic conditions, pyruvate enters mitochondria via the mitochondrial pyruvate carrier (MPC) and is converted to acetyl-CoA by pyruvate dehydrogenase. Under hypoxia, lactate dehydrogenase reduces pyruvate to lactate, regenerating NAD+.
  • •Glycolysis is regulated allosterically at PFK-1 and pyruvate kinase, hormonally via glucagon/insulin on PFKFB2, and transcriptionally by HIF-1α (hypoxia), c-Myc, and p53. Post-translational control includes APC/C-Cdh1-mediated degradation of PFKFB3 during cell cycle.

Clinical Relevance

  • •Suspect an inborn error of glycolysis in any patient with unexplained hemolytic anemia, exercise-induced rhabdomyolysis, or neonatal cholestasis with hyperammonemia. Ask about family history, triggers (fever, fasting, oxidant drugs), and response to exercise.
  • •For hemolytic anemia, order a G6PD activity assay and consider pyruvate kinase deficiency if G6PD is normal. A fluorescent spot test or quantitative assay can confirm G6PD deficiency.
  • •For rhabdomyolysis with exercise, check aldolase A activity and consider phosphofructokinase (Tarui disease) or phosphorylase deficiency (McArdle). Aldolase A deficiency presents with acute rhabdomyolysis triggered by fever or exercise.
  • •For neonatal cholestasis with hyperammonemia, suspect citrin deficiency (SLC25A13 mutation). Order plasma amino acids (elevated citrulline, arginine) and ammonia. Newborn screening may identify elevated citrulline.
  • •In citrin deficiency, initiate medium-chain triglycerides (MCT) at ≈20-30% of total caloric intake, divided with meals. MCT bypasses the defective malate-aspartate shuttle by providing an alternative mitochondrial fuel. Avoid intravenous fructose and persistent hyperglycemia.
  • •In PGM1-CDG (cleft palate, hypoglycemia, cardiomyopathy), start d-galactose 1-2 g/kg/day in divided doses. Early diagnosis prevents irreversible cardiomyopathy and improves glycosylation.
  • •In lactic acidosis, measure lactate and pyruvate to calculate the lactate-to-pyruvate ratio. A ratio >25 (with elevated lactate) suggests mitochondrial disease or pyruvate dehydrogenase deficiency; a ratio <10 suggests increased glycolytic flux (e.g., hypoxia, exercise, cancer).
  • •Treat lactic acidosis by addressing the underlying cause: manage sepsis with source control and antibiotics; correct hypoperfusion with fluids and vasopressors; consider thiamine (vitamin B1) 100-200 mg IV daily if deficiency is suspected.
  • •In cancer, the Warburg effect is driven by HIF-1α, c-Myc, and loss of p53. Consider FDG-PET to assess glycolytic activity; total lesion glycolysis (TLG) predicts survival in cervical cancer and others.
  • •Therapeutic targeting of glycolysis in cancer includes inhibitors of GLUT1, hexokinase 2 (HK2), PFKFB3, lactate dehydrogenase A (LDHA), and monocarboxylate transporters (MCT1/4). Combination with immune checkpoint blockade or chemotherapy is under investigation.
  • •Ketogenic diet (low carbohydrate, high fat) as adjunctive therapy for glioblastoma exploits glucose dependency; adherent patients have shown median OS of 29.4 months in early studies, with no grade 3/4 diet-related toxicities.
  • •Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with known glycolytic enzyme defects because they may impair myocardial metabolism. Also avoid oxidant drugs (sulfonamides, dapsone, nitrofurantoin) in G6PD deficiency.

Board Review — High Yield

  • •PFK-1, Rate-limiting step of glycolysis; activated by fructose-2,6-bisphosphate and AMP; inhibited by ATP and citrate.
  • •Pyruvate kinase deficiency, Chronic hemolytic anemia due to defect in the last glycolytic step; treated with splenectomy and allogeneic stem cell transplant.
  • •G6PD deficiency, Most common glycolytic pathway defect (~400 million worldwide); causes hemolytic anemia after oxidative stress (sulfa drugs, fava beans); X-linked.
  • •Lactate-to-pyruvate ratio >25, Suggests impaired mitochondrial oxidation (e.g., respiratory chain defects, pyruvate dehydrogenase deficiency).
  • •Warburg effect, Aerobic glycolysis in cancer cells even in the presence of oxygen; driven by HIF-1α, c-Myc, and p53 loss; exploited for FDG-PET imaging.
  • •Citrin deficiency (SLC25A13), Malate-aspartate shuttle defect causing neonatal cholestasis and adult hyperammonemia; treat with MCT oil; avoid IV fructose.
  • •PGM1-CDG, Congenital disorder of glycosylation with cleft palate, hypoglycemia, cardiomyopathy; treatable with d-galactose.
  • •Phosphoglycerate mutase (dPGM), Requires 2,3-BPG as cofactor; member of histidine phosphatase superfamily.
  • •Glycolysis in erythrocytes, Only energy source; produces lactate obligatorily; net 2 ATP per glucose.
  • •Lactate as signaling molecule, Acts via lysine lactylation and N-lactoyl amino acids to regulate gene expression and immune function.

Deep Dive — Evidence Details

References

  1. [1]

    Altassan R, Radenkovic S, Edmondson AC et al.. “International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management.” Journal of inherited metabolic disease (2020). PMID: 32681750 ↗

    L1GUIDELINECited in: Definition & Overview, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  2. [2]

    Rabinowitz JD, Enerbäck S. “Lactate: the ugly duckling of energy metabolism.” Nature metabolism (2020). PMID: 32694798 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Energetics & Stoichiometry
  3. [3]

    TeSlaa T, Ralser M, Fan J et al.. “The pentose phosphate pathway in health and disease.” Nature metabolism (2023). PMID: 37612403 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Summary, Pearls & Key Takeaways
  4. [4]

    Cunnane SC, Trushina E, Morland C et al.. “Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing.” Nature reviews. Drug discovery (2020). PMID: 32709961 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation, Summary, Pearls & Key Takeaways
  5. [5]

    Hamel Y, Mamoune A, Mauvais FX et al.. “Acute rhabdomyolysis and inflammation.” Journal of inherited metabolic disease (2015). PMID: 25778939 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  6. [6]

    Saudubray JM, Sedel F, Walter JH. “Clinical approach to treatable inborn metabolic diseases: an introduction.” Journal of inherited metabolic disease (2006). PMID: 16763886 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  7. [7]

    Linster CL, Veiga-da-Cunha M, Niehaus TD et al.. “Metabolite Damage and Repair in Health and Disease.” Annual review of nutrition (2026). PMID: 42207943 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Regulation
  8. [8]

    Trayhurn P. “Hypoxia and adipocyte physiology: implications for adipose tissue dysfunction in obesity.” Annual review of nutrition (2014). PMID: 24819450 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes
  9. [9]

    Goyal MS, Hawrylycz M, Miller JA et al.. “Aerobic glycolysis in the human brain is associated with development and neotenous gene expression.” Cell metabolism (2014). PMID: 24411938 ↗

    L1SR_OBSCited in: Definition & Overview, Regulation
  10. [10]

    Xiao S, Markhard AL, Long JZ. “Lactate as a Chemical Modification on Proteins and Metabolites.” Annual review of biochemistry (2026). PMID: 42331744 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation, Summary, Pearls & Key Takeaways
  11. [11]

    Lee P, Chandel NS, Simon MC. “Cellular adaptation to hypoxia through hypoxia inducible factors and beyond.” Nature reviews. Molecular cell biology (2020). PMID: 32144406 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Energetics & Stoichiometry
  12. [12]

    Ito K, Suda T. “Metabolic requirements for the maintenance of self-renewing stem cells.” Nature reviews. Molecular cell biology (2014). PMID: 24651542 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Regulation
  13. [13]

    Srinivas T, Hanumaiah G, Nagendra D et al.. “Immunometabolic reprogramming and mitochondrial dysfunction in acute respiratory distress syndrome: mechanisms, metabolic resilience, and therapeutic perspectives- a narrative review.” Journal of translational medicine (2026). PMID: 42432720 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation, Energetics & Stoichiometry, Summary, Pearls & Key Takeaways
  14. [14]

    Lu X, Zhao Y, Qin P et al.. “Metabolic reprogramming of macrophages during mycobacterial infection: a review of immunometabolic crosstalk and pathogen manipulation.” Frontiers in cellular and infection microbiology (2026). PMID: 42422378 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes
  15. [15]

    Zhang Y, Zhang J, Cao Y. “The lactate-lactylation axis in tumor radioresistance: metabolic, epigenetic, and immune mechanisms with emerging links to RNA regulation.” Frontiers in immunology (2026). PMID: 42421972 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation
  16. [16]

    Zhou L, Jiang Y, Luo J et al.. “Metabolic regulation of macrophage polarization in myocardial infarction: from mechanisms to targeted therapies.” Journal of translational medicine (2026). PMID: 42415091 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Regulation, Cofactors, Vitamins & Micronutrient Dependencies
  17. [17]

    Kierans SJ, Taylor CT. “Glycolysis: A multifaceted metabolic pathway and signaling hub.” The Journal of biological chemistry (2024). PMID: 39442619 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Energetics & Stoichiometry, Summary, Pearls & Key Takeaways
  18. [18]

    Reddan B, Cummins EP. “The regulation of cell metabolism by hypoxia and hypercapnia.” The Journal of biological chemistry (2025). PMID: 39914740 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation
  19. [19]

    Flood D, Lee ES, Taylor CT. “Intracellular energy production and distribution in hypoxia.” The Journal of biological chemistry (2023). PMID: 37507013 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Energetics & Stoichiometry, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Summary, Pearls & Key Takeaways
  20. [20]

    Loftus RM, Finlay DK. “Immunometabolism: Cellular Metabolism Turns Immune Regulator.” The Journal of biological chemistry (2015). PMID: 26534957 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation, Summary, Pearls & Key Takeaways
  21. [21]

    Pavlova NN, Thompson CB. “The Emerging Hallmarks of Cancer Metabolism.” Cell metabolism (2016). PMID: 26771115 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation
  22. [22]

    Brooks GA. “The Science and Translation of Lactate Shuttle Theory.” Cell metabolism (2018). PMID: 29617642 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Summary, Pearls & Key Takeaways
  23. [23]

    Vitale I, Manic G, Coussens LM et al.. “Macrophages and Metabolism in the Tumor Microenvironment.” Cell metabolism (2019). PMID: 31269428 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation
  24. [24]

    Thornton C, Grad E, Yaka R. “The role of mitochondria in cocaine addiction.” The Biochemical journal (2021). PMID: 33626141 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation
  25. [25]

    McCommis KS, Finck BN. “Mitochondrial pyruvate transport: a historical perspective and future research directions.” The Biochemical journal (2015). PMID: 25748677 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview
  26. [26]

    Igamberdiev AU, Kleczkowski LA. “Pyrophosphate as an alternative energy currency in plants.” The Biochemical journal (2021). PMID: 33881486 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview
  27. [27]

    Karwi QG, Jörg AR, Lopaschuk GD. “Allosteric, transcriptional and post-translational control of mitochondrial energy metabolism.” The Biochemical journal (2019). PMID: 31217327 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation, Cofactors, Vitamins & Micronutrient Dependencies, Summary, Pearls & Key Takeaways
  28. [28]

    Patra KC, Hay N. “The pentose phosphate pathway and cancer.” Trends in biochemical sciences (2014). PMID: 25037503 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Pathway Steps & Enzymes, Regulation, Summary, Pearls & Key Takeaways
  29. [29]

    Icard P, Fournel L, Wu Z et al.. “Interconnection between Metabolism and Cell Cycle in Cancer.” Trends in biochemical sciences (2019). PMID: 30655165 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview
  30. [30]

    Ippolito L, Morandi A, Giannoni E et al.. “Lactate: A Metabolic Driver in the Tumour Landscape.” Trends in biochemical sciences (2018). PMID: 30473428 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Regulation, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Summary, Pearls & Key Takeaways
  31. [31]

    Bryant KL, Mancias JD, Kimmelman AC et al.. “KRAS: feeding pancreatic cancer proliferation.” Trends in biochemical sciences (2014). PMID: 24388967 ↗

    L5REVIEW_NARRATIVECited in: Definition & Overview, Summary, Pearls & Key Takeaways
  32. [32]

    Xie K, Sun Y, Li X et al.. “Biomarkers and pathways in autism spectrum disorder: An individual meta-analysis based on proteomic and metabolomic data.” European archives of psychiatry and clinical neuroscience (2024). PMID: 39361099 ↗

    L1SR_OBSCited in: Molecular Structure & Components
  33. [33]

    Ademi A, Topi S, Gugu M et al.. “Oral Barrier Immunometabolism in Chronic Low-Grade Inflammation: Molecular Mechanisms and Systemic Implications.” International journal of molecular sciences (2026). PMID: 42353075 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components
  34. [34]

    Kwon P, Wang Y, Zhou J et al.. “Enzymatic depolymerization of polyurethanes: discovery, mechanisms, and engineering of hydrolases.” Bioresource technology (2026). PMID: 42331188 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components
  35. [35]

    Xiao K, Gu L, Ma J et al.. “High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.” Chinese medical journal (2026). PMID: 42156155 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components
  36. [36]

    Liu H, Yao Y, Zhang C et al.. “Metabolic Checkpoints in IgA Nephropathy: From Pathogenesis to Precision Medicine.” Drugs (2026). PMID: 41618071 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components
  37. [37]

    Harold KM, Yoon WH, Humphries KM. “Orchestrating glucose metabolism: PFKFB2 as a signal-integrating conductor in homeostasis and disease.” The Journal of biological chemistry (2026). PMID: 42349790 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components, Pathway Steps & Enzymes, Regulation
  38. [38]

    Rigden DJ. “The histidine phosphatase superfamily: structure and function.” The Biochemical journal (2008). PMID: 18092946 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components, Cofactors, Vitamins & Micronutrient Dependencies, Summary, Pearls & Key Takeaways
  39. [39]

    Lacabanne D, Ruprecht JJ, Sichrovsky M et al.. “Structural transport and inhibition mechanism of the mitochondrial pyruvate carrier.” Trends in biochemical sciences (2025). PMID: 41353022 ↗

    L5REVIEW_NARRATIVECited in: Molecular Structure & Components
  40. [40]

    Broeks MH, van Karnebeek CDM, Wanders RJA et al.. “Inborn disorders of the malate aspartate shuttle.” Journal of inherited metabolic disease (2021). PMID: 33990986 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Energetics & Stoichiometry, Cofactors, Vitamins & Micronutrient Dependencies, Summary, Pearls & Key Takeaways
  41. [41]

    Mucumbitsi J, Hakizimana JC, Kampire MG et al.. “The role of trained immunity in chronic non-communicable inflammatory diseases.” Innate immunity (2026). PMID: 42017903 ↗

    L2SR_OBSCited in: Pathway Steps & Enzymes
  42. [42]

    Buchakjian MR, Kornbluth S. “The engine driving the ship: metabolic steering of cell proliferation and death.” Nature reviews. Molecular cell biology (2010). PMID: 20861880 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  43. [43]

    Lee IG, Jung K. “Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.” Experimental & molecular medicine (2026). PMID: 42380285 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  44. [44]

    Narayanasamy A, Karuppusamy PA, Gnanarajan R et al.. “Mechanobiology-Driven Metabolic Reprogramming: Integrative Roles of YAP/TAZ Signaling and Extracellular Matrix Dynamics.” Cell biology international (2026). PMID: 42370757 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Integration with Whole-body Metabolism
  45. [45]

    Xu Z, Shi F, Han J et al.. “Hijacking and subversion of macrophage antiviral functions by viruses.” Virulence (2026). PMID: 42370645 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  46. [46]

    Lenzen S. “A fresh view of glycolysis and glucokinase regulation: history and current status.” The Journal of biological chemistry (2014). PMID: 24637025 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Regulation
  47. [47]

    Bachmann AS, Geerts D. “Polyamine synthesis as a target of MYC oncogenes.” The Journal of biological chemistry (2018). PMID: 30404920 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  48. [48]

    Foster DA, Salloum D, Menon D et al.. “Phospholipase D and the maintenance of phosphatidic acid levels for regulation of mammalian target of rapamycin (mTOR).” The Journal of biological chemistry (2014). PMID: 24990952 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  49. [49]

    Aslan S, Noor E, Bar-Even A. “Holistic bioengineering: rewiring central metabolism for enhanced bioproduction.” The Biochemical journal (2017). PMID: 29146872 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  50. [50]

    Ralser M. “An appeal to magic? The discovery of a non-enzymatic metabolism and its role in the origins of life.” The Biochemical journal (2018). PMID: 30166494 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  51. [51]

    Fernandez-Fernandez S, Almeida A, Bolaños JP. “Antioxidant and bioenergetic coupling between neurons and astrocytes.” The Biochemical journal (2012). PMID: 22417747 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Regulation
  52. [52]

    Moncada S, Higgs EA, Colombo SL. “Fulfilling the metabolic requirements for cell proliferation.” The Biochemical journal (2012). PMID: 22835215 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Regulation
  53. [53]

    Fitzpatrick TB, Amrhein N, Kappes B et al.. “Two independent routes of de novo vitamin B6 biosynthesis: not that different after all.” The Biochemical journal (2007). PMID: 17822383 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Cofactors, Vitamins & Micronutrient Dependencies, Comparison, Distinctions & Common Confusions
  54. [54]

    Compton JA, Patrick WM. “The more we learn, the more diverse it gets: structures, functions and evolution in the Phosphofructokinase Superfamily.” The Biochemical journal (2025). PMID: 40329473 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Regulation
  55. [55]

    Bolaños JP, Almeida A, Moncada S. “Glycolysis: a bioenergetic or a survival pathway?” Trends in biochemical sciences (2009). PMID: 20006513 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Regulation
  56. [56]

    Calejman CM, Doxsey WG, Fazakerley DJ et al.. “Integrating adipocyte insulin signaling and metabolism in the multi-omics era.” Trends in biochemical sciences (2022). PMID: 35304047 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes
  57. [57]

    Bommer GT, Van Schaftingen E, Veiga-da-Cunha M. “Metabolite Repair Enzymes Control Metabolic Damage in Glycolysis.” Trends in biochemical sciences (2019). PMID: 31473074 ↗

    L5REVIEW_NARRATIVECited in: Pathway Steps & Enzymes, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  58. [58]

    Kruiswijk F, Labuschagne CF, Vousden KH. “p53 in survival, death and metabolic health: a lifeguard with a licence to kill.” Nature reviews. Molecular cell biology (2015). PMID: 26122615 ↗

    L5REVIEW_NARRATIVECited in: Regulation
  59. [59]

    Sun W, Huang H, Lan X et al.. “Brain-muscle axis regulation of neuroinflammation and sarcopenia in Parkinson's disease: the bridging role of lactylation.” Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (2026). PMID: 42400678 ↗

    L5REVIEW_NARRATIVECited in: Regulation
  60. [60]

    Mou C, Wang Y, Kim MY et al.. “Ginsenosides from Panax ginseng: Their mechanisms, microbiome determinants, and translational strategies in therapeutic activity against cancer.” Journal of ginseng research (2026). PMID: 42395025 ↗

    L5REVIEW_NARRATIVECited in: Regulation, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  61. [61]

    Di Carlo E. “Targeting the cancer metabolism-immunity interface: update and perspectives.” Experimental hematology & oncology (2026). PMID: 42393797 ↗

    L5REVIEW_NARRATIVECited in: Regulation, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  62. [62]

    Wheeler MA, Rothhammer V, Quintana FJ. “Control of immune-mediated pathology via the aryl hydrocarbon receptor.” The Journal of biological chemistry (2017). PMID: 28615443 ↗

    L5REVIEW_NARRATIVECited in: Regulation
  63. [63]

    Schmidt CA, Fisher-Wellman KH, Neufer PD. “From OCR and ECAR to energy: Perspectives on the design and interpretation of bioenergetics studies.” The Journal of biological chemistry (2021). PMID: 34461088 ↗

    L5REVIEW_NARRATIVECited in: Regulation, Energetics & Stoichiometry
  64. [64]

    Koo JH, Guan KL. “Interplay between YAP/TAZ and Metabolism.” Cell metabolism (2018). PMID: 30089241 ↗

    L5REVIEW_NARRATIVECited in: Regulation, Summary, Pearls & Key Takeaways
  65. [65]

    DeBerardinis RJ, Lum JJ, Hatzivassiliou G et al.. “The biology of cancer: metabolic reprogramming fuels cell growth and proliferation.” Cell metabolism (2008). PMID: 18177721 ↗

    L5REVIEW_NARRATIVECited in: Regulation, Summary, Pearls & Key Takeaways
  66. [66]

    Longo J, Watson MJ, Williams KS et al.. “Nutrient allocation fuels T cell-mediated immunity.” Cell metabolism (2025). PMID: 41101312 ↗

    L5REVIEW_NARRATIVECited in: Regulation
  67. [67]

    Haas R, Cucchi D, Smith J et al.. “Intermediates of Metabolism: From Bystanders to Signalling Molecules.” Trends in biochemical sciences (2016). PMID: 26935843 ↗

    L5REVIEW_NARRATIVECited in: Regulation
  68. [68]

    Johnson RF, Perkins ND. “Nuclear factor-κB, p53, and mitochondria: regulation of cellular metabolism and the Warburg effect.” Trends in biochemical sciences (2012). PMID: 22626470 ↗

    L5REVIEW_NARRATIVECited in: Regulation
  69. [69]

    Vuković T, Kuek LE, Yu B et al.. “The therapeutic landscape of citrin deficiency.” Journal of inherited metabolic disease (2024). PMID: 39021261 ↗

    L5REVIEW_NARRATIVECited in: Energetics & Stoichiometry, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Summary, Pearls & Key Takeaways
  70. [70]

    Hayasaka K. “Metabolic basis and treatment of citrin deficiency.” Journal of inherited metabolic disease (2020). PMID: 32740958 ↗

    L5REVIEW_NARRATIVECited in: Energetics & Stoichiometry, Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  71. [71]

    Ramezan M, Demetriou A, Burke SN et al.. “Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.” Alzheimer's & dementia : the journal of the Alzheimer's Association (2026). PMID: 42271173 ↗

    L5REVIEW_NARRATIVECited in: Energetics & Stoichiometry
  72. [72]

    Wang Y, Lu Y, Zhou J et al.. “Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.” Clinical and translational medicine (2026). PMID: 42163583 ↗

    L5REVIEW_NARRATIVECited in: Energetics & Stoichiometry
  73. [73]

    Lu MF, Qi XY, Cheng JW et al.. “The application of low-carbohydrate diet in autoimmune diseases: Mechanisms, evidence, and prospects for clinical translation.” Autoimmunity reviews (2026). PMID: 42061668 ↗

    L5REVIEW_NARRATIVECited in: Energetics & Stoichiometry
  74. [74]

    Liao J, Ji Q. “Fueling the fatal voyage: How metabolic plasticity empowers every step of cancer metastasis.” Cancer letters (2026). PMID: 41912134 ↗

    L5REVIEW_NARRATIVECited in: Energetics & Stoichiometry
  75. [75]

    Firdous J, Asif AE, Haris HM et al.. “Efficacy and safety of ketogenic diet in glioblastoma: an updated systematic review and meta-analysis.” Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology (2026). PMID: 42032215 ↗

    L2SR_OBSCited in: Integration with Whole-body Metabolism
  76. [76]

    Long Y, Xu J, Xu Z et al.. “The Warburg effect and beyond: Glycolytic reprogramming in cancer progression and emerging therapeutic strategies.” Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2026). PMID: 42320368 ↗

    L5REVIEW_NARRATIVECited in: Integration with Whole-body Metabolism
  77. [77]

    Gao C, Chen J, Pang B et al.. “The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.” Translational lung cancer research (2026). PMID: 42291355 ↗

    L5REVIEW_NARRATIVECited in: Integration with Whole-body Metabolism
  78. [78]

    Yao YZ, Yin T, Yao YM. “Platelet Mitochondria: A Promising Target for Antiplatelet Therapy.” Antioxidants & redox signaling (2026). PMID: 42203635 ↗

    L5REVIEW_NARRATIVECited in: Integration with Whole-body Metabolism
  79. [79]

    Olson KA, Schell JC, Rutter J. “Pyruvate and Metabolic Flexibility: Illuminating a Path Toward Selective Cancer Therapies.” Trends in biochemical sciences (2016). PMID: 26873641 ↗

    L5REVIEW_NARRATIVECited in: Integration with Whole-body Metabolism
  80. [80]

    Masutin V, Kersch C, Schmitz-Spanke S. “A systematic review: metabolomics-based identification of altered metabolites and pathways in the skin caused by internal and external factors.” Experimental dermatology (2022). PMID: 35030266 ↗

    L5SR_OBSCited in: Cofactors, Vitamins & Micronutrient Dependencies, Comparison, Distinctions & Common Confusions
  81. [81]

    Mirabile A, Rivoltini L, Daveri E et al.. “Metabolism and Immune Modulation in Patients with Solid Tumors: Systematic Review of Preclinical and Clinical Evidence.” Cancers (2020). PMID: 32375310 ↗

    L5SR_OBSCited in: Cofactors, Vitamins & Micronutrient Dependencies
  82. [82]

    Chen G, Chen Y, Chu C et al.. “Metabolism-driven emerging acylation modifications in COPD: from elucidation of fundamental mechanisms to clinical diagnosis and treatment.” Frontiers in immunology (2026). PMID: 42199440 ↗

    L5REVIEW_NARRATIVECited in: Cofactors, Vitamins & Micronutrient Dependencies
  83. [83]

    Błaszczyk JW. “Degradation of the Molecular Basis of Life During the Aging Process.” International journal of molecular sciences (2026). PMID: 41828636 ↗

    L5REVIEW_NARRATIVECited in: Cofactors, Vitamins & Micronutrient Dependencies
  84. [84]

    Eckle SB, Corbett AJ, Keller AN et al.. “Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells.” The Journal of biological chemistry (2015). PMID: 26468291 ↗

    L5REVIEW_NARRATIVECited in: Cofactors, Vitamins & Micronutrient Dependencies
  85. [85]

    Igamberdiev AU, Kleczkowski LA. “Magnesium and cell energetics in plants under anoxia.” The Biochemical journal (2011). PMID: 21749322 ↗

    L5REVIEW_NARRATIVECited in: Cofactors, Vitamins & Micronutrient Dependencies
  86. [86]

    Häberle J. “Citrin deficiency-The East-side story.” Journal of inherited metabolic disease (2024). PMID: 38994653 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Summary, Pearls & Key Takeaways
  87. [87]

    Zhang B, Wang N, Wang X et al.. “Herb-derived immunometabolic modulators: traditional Chinese medicine at the crossroads of metabolism and antitumor immunity.” Chinese medicine (2026). PMID: 42363193 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  88. [88]

    Yu G, Ge W, Yao H et al.. “Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications.” Oncology research (2026). PMID: 42358827 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  89. [89]

    Iova OM, Marin GE, Răzniceanu V et al.. “Targeting the Warburg Effect in Anaplastic Thyroid Carcinoma: Metabolic Vulnerabilities and Therapeutic Opportunities.” International journal of molecular sciences (2026). PMID: 42353188 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  90. [90]

    Wang K, Lu H, Deng N et al.. “Targeting the KMT2D-driven Enhancer-Immune-Metabolic axis in HNSCC: Reconciling the paradox for precision therapy.” Biochimica et biophysica acta. Reviews on cancer (2026). PMID: 42349694 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  91. [91]

    Fu J, Dai Y, Wang Q et al.. “Glycolytic reprogramming in ovarian cancer: mechanisms, immune crosstalk, and therapeutic implications.” Frontiers in immunology (2026). PMID: 42317327 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets
  92. [92]

    Kopel JJ, Bhutia YD, Sivaprakasam S et al.. “Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier.” The Biochemical journal (2021). PMID: 33544126 ↗

    L5REVIEW_NARRATIVECited in: Clinical Correlation: Inborn Errors, Biomarkers & Drug Targets, Comparison, Distinctions & Common Confusions
  93. [93]

    Ribeiro GBES, Rodrigues FR, Pasqualotto E et al.. “Exposure to Glycolysis-Enhancing Drugs and Risk of Parkinson's Disease: A Meta-Analysis.” Journal of Parkinson's disease (2024). PMID: 39031384 ↗

    L2SR_OBSCited in: Comparison, Distinctions & Common Confusions
  94. [94]

    Abu Bakar MF, Chin SF, Makpol S et al.. “Diagnostic performance of serum metabolites biomarker associated with colorectal adenoma: a systematic review.” PeerJ (2024). PMID: 39314843 ↗

    L3SR_OBSCited in: Comparison, Distinctions & Common Confusions
  95. [95]

    Krawczyk M, Burzynska-Pedziwiatr I, Wozniak LA et al.. “Evidence from a Systematic Review and Meta-Analysis Pointing to the Antidiabetic Effect of Polyphenol-Rich Plant Extracts from Gymnema montanum, Momordica charantia and Moringa oleifera.” Current issues in molecular biology (2022). PMID: 35723334 ↗

    L5SR_OBSCited in: Comparison, Distinctions & Common Confusions
  96. [96]

    Fung TS, Chakrabarti R, Higgs HN. “The multiple links between actin and mitochondria.” Nature reviews. Molecular cell biology (2023). PMID: 37277471 ↗

    L5REVIEW_NARRATIVECited in: Summary, Pearls & Key Takeaways
  97. [97]

    Wei W, Ku D, Rutherford N. “Prognostic Value of Combined FDG PET and MRI Analysis of Cervical Cancer: A Systematic Review and Meta-Analysis.” Journal of medical radiation sciences (2026). PMID: 42316916 ↗

    L2SR_OBSCited in: Summary, Pearls & Key Takeaways
  98. [98]

    Wasem VL, Mookerjee SA. “A bioenergetic understanding of "aerobic glycolysis".” Communications biology (2026). PMID: 42426135 ↗

    L5REVIEW_NARRATIVECited in: Summary, Pearls & Key Takeaways
  99. [99]

    Llibre A, Grudzinska FS, O'Shea MK et al.. “Lactate cross-talk in host-pathogen interactions.” The Biochemical journal (2021). PMID: 34492096 ↗

    L5REVIEW_NARRATIVECited in: Summary, Pearls & Key Takeaways

Revision History

All updates applied to this page

Loading revisions…