The return of metabolism: biochemistry and physiology of glycolysis.

Journal: Biological reviews of the Cambridge Philosophical Society
Published Date: Nov 30, 2025

Abstract

Glycolysis is a fundamental metabolic pathway central to the bioenergetics and physiology of virtually all living organisms. In this comprehensive review, we explore the intricate biochemical principles and evolutionary origins of glycolytic pathways, from the classical Embden-Meyerhof-Parnas (EMP) pathway in humans to various prokaryotic and alternative glycolytic routes. By examining glycolysis across the tree of life, we explore its presence and adaptation in prokaryotes, archaea, bacteria, animals and plants, and the extension of glycolysis into sulfosugar metabolism. Further, we discuss the role of unwanted side reactions, thermodynamic principles, and metabolic control principles that underpin glycolysis and the broader metabolic network, and summarise advanced methods for quantifying glycolytic activity, including new analytical methods, alongside kinetic, constraint-based, and machine-learning based modelling. With a focus on the Pasteur, Crabtree, and Warburg effects, this review further discusses the roles of glycolysis in health and disease, highlighting its impact on global metabolic operations, inborn errors, and various pathologies as well as its role in biotechnology and metabolic engineering.

Authors

  • Nana-Maria Grüning
    Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Charitéplatz 1, Berlin, 10117, Germany.
  • Federica Agostini
    Center for Chronic Intestinal Failure, St Orsola Hospital, University of Bologna, Bologna, Italy; School of Medicine of the University of Bologna, Bologna, Italy.
  • Camila Caldana
    Max Planck Institute of Molecular Plant Physiology, Am Mühlenberg 1, Potsdam-Golm, 14476, Germany.
  • Johannes Hartl
    Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
  • Matthias Heinemann
    University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Nijenborgh 7, Groningen, 9747 AG, The Netherlands.
  • Markus A Keller
    Medical University of Innsbruck, Institute of Human Genetics, Peter-Mayr-Str. 1, Innsbruck, 6020, Austria.
  • Jan Lukas Krüsemann
    Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Charitéplatz 1, Berlin, 10117, Germany.
  • Costanza Lamperti
    Division of Medical Genetics and Neurogenetics, Fondazione IRCCS Neurological Institute 'C. Besta', Via Temolo 4, Milano, 20126, Italy.
  • Carole L Linster
    Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 7 avenue des Hauts-Fourneaux, Esch-sur-Alzette, L-4362, Luxembourg.
  • Steffen N Lindner
    Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Charitéplatz 1, Berlin, 10117, Germany.
  • Julia Muenzner
    Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Charitéplatz 1, Berlin, 10117, Germany.
  • Jens Nielsen
    Department of Biology and Biological Engineering , Chalmers University of Technology , SE-412 96 Gothenburg , Sweden.
  • Zoran Nikoloski
    Bioinformatics Group, Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany; Bioinformatics and Mathematical Modeling Department, Centre for Plant Systems Biology and Biotechnology, Plovdiv, Bulgaria; Systems Biology and Mathematical Modeling Group, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany. Electronic address: [email protected].
  • Bettina Siebers
    Molecular Enzyme Technology and Biochemistry (MEB), Environmental Microbiology and Biotechnology (EMB), Centre for Water and Environmental Research (CWE), Department of Chemistry, University of Duisburg-Essen, Universitätsstrasse 5, Essen, 45141, Germany.
  • Jacky L Snoep
    Stellenbosch University, Department of Biochemistry, P.O. Box X1, Stellenbosch, 7599, South Africa.
  • Hezi Tenenboim
    Charité - Universitätsmedizin Berlin, Institute of Biochemistry, Charitéplatz 1, Berlin, 10117, Germany.
  • Bas Teusink
    Vrije Universiteit Amsterdam, Systems Biology Lab, AIMMS/A-LIFE, De Boelelaan 1085 HV, Amsterdam, 1081, The Netherlands.
  • Spencer J Williams
    University of Melbourne, School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, 3010, Victoria, Australia.
  • Mirjam M C Wamelink
    Amsterdam University Medical Center (UMC), location Academic Medical Center (AMC), Laboratory Genetic Metabolic Diseases, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
  • Markus Ralser
    The Francis Crick Institute, Molecular Biology of Metabolism laboratory, London, UK. [email protected].

Keywords

No keywords available for this article.

External Resources

Popular Topics
Recent Journals