The return of metabolism: biochemistry and physiology of glycolysis
Journal article, 2026
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.
thermodynamics
biochemical pathway
Warburg effect
energy metabolism
computational modelling
metabolic diseases
Pasteur effect
metabolic regulation
glycolysis
Crabtree effect
Author
Nana-Maria Grüning
Charité University Medicine Berlin
Federica Agostini
Charité University Medicine Berlin
Camila Caldana
Max Planck Society
Johannes Hartl
Charité University Medicine Berlin
Matthias Heinemann
University of Groningen
M. A. Keller
Medical University of Innsbruck
Jan Lukas Krusemann
Max Planck Society
Charité University Medicine Berlin
Costanza Lamperti
Carlo Besta Neurological Institute
Carole L. Linster
University of Luxembourg
Steffen N. Lindner
Charité University Medicine Berlin
Julia Muenzner
Charité University Medicine Berlin
Jens B Nielsen
BioInnovation Institute
Chalmers, Life Sciences, Systems and Synthetic Biology
Zoran Nikoloski
Max Planck Society
University of Potsdam
Bettina Siebers
University of Duisburg-Essen
J. L. Snoep
Vrije Universiteit Amsterdam
Stellenbosch University
Hezi Tenenboim
Charité University Medicine Berlin
B. Teusink
Vrije Universiteit Amsterdam
Spencer J. Williams
University of Melbourne
Mirjam M.C. Wamelink
University of Amsterdam
M. Ralser
University of Oxford
Max Planck Society
Biological Reviews
1464-7931 (ISSN) 1469185x (eISSN)
Vol. 101 2 751-803Subject Categories (SSIF 2025)
Molecular Biology
Cancer and Oncology
DOI
10.1111/brv.70104
PubMed
41319207