The return of metabolism: biochemistry and physiology of glycolysis
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
- Mirjam M. C. Wamelink (ORCID: https://orcid.org/0000-0002-9382-613X)
- Bettina Siebers (ORCID: https://orcid.org/0000-0002-9905-541X)
- Steffen N. Lindner (ORCID: https://orcid.org/0000-0003-3226-3043)
- Jacky L. Snoep (ORCID: https://orcid.org/0000-0002-0405-8854)
- Spencer J. Williams (ORCID: https://orcid.org/0000-0001-6341-4364)
- Jan Lukas Krüsemann (ORCID: https://orcid.org/0000-0002-7829-3881)
- Camila Caldana (ORCID: https://orcid.org/0000-0003-3639-0621)
- Matthias Heinemann (ORCID: https://orcid.org/0000-0002-5512-9077)
- Hezi Tenenboim (ORCID: https://orcid.org/0000-0002-3783-9446)
- Markus A. Keller (ORCID: https://orcid.org/0000-0002-8654-9920)
- Federica Agostini (ORCID: https://orcid.org/0000-0002-4255-4867)
- Johannes Hartl (ORCID: https://orcid.org/0000-0001-8470-5355)
- Carole L. Linster (ORCID: https://orcid.org/0000-0001-7143-0719)
- Costanza Lamperti (ORCID: https://orcid.org/0000-0002-2280-2253)
- Julia Muenzner (ORCID: https://orcid.org/0000-0002-5402-5890)
- Nana‐Maria Grüning (ORCID: https://orcid.org/0000-0002-1528-6625)
- Zoran Nikoloski (ORCID: https://orcid.org/0000-0003-2671-6763)
- Markus Ralser (ORCID: https://orcid.org/0000-0001-9535-7413)
- Bas Teusink (ORCID: https://orcid.org/0000-0003-3929-0423)
- Jens Nielsen (ORCID: https://orcid.org/0000-0002-6522-9987)
Institutions
- Centre for Human Genetics (GB)
- Innsbruck Medical University (AT)
- The University of Melbourne (AU)
- University of Groningen (NL)
- University of Potsdam (DE)
- University of Luxembourg (LU)
- Universität Innsbruck (AT)
- Stellenbosch University (ZA)
- Amsterdam UMC Location University of Amsterdam (NL)
- Max Planck Institute of Molecular Plant Physiology (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- Max Planck Institute for Molecular Genetics (DE)
- BioInnovation Institute (DK)
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Max Planck Institute for Terrestrial Microbiology (DE)
- University of Duisburg-Essen (DE)
- Chalmers University of Technology (SE)
- Charité - Universitätsmedizin Berlin (DE)
- Vrije Universiteit Amsterdam (NL)
- University of Amsterdam (NL)
Publication Details
- Journal
- Biological reviews/Biological reviews of the Cambridge Philosophical Society
- Published
- 2025-11-30
- DOI
- https://doi.org/10.1111/brv.70104
- Citations
- 4
- Primary Topic
- Microbial Metabolic Engineering and Bioproduction
- Type
- article
- Field-Weighted Citation Impact
- 3.22