Glucose feeds the tricarboxylic acid cycle via excreted ethanol in fermenting yeast. Author Tianxia Xiao, Artem Khan, Yihui Shen, Li Chen, Joshua Rabinowitz Publication Year 2022 Type Journal Article Abstract Ethanol and lactate are typical waste products of glucose fermentation. In mammals, glucose is catabolized by glycolysis into circulating lactate, which is broadly used throughout the body as a carbohydrate fuel. Individual cells can both uptake and excrete lactate, uncoupling glycolysis from glucose oxidation. Here we show that similar uncoupling occurs in budding yeast batch cultures of Saccharomyces cerevisiae and Issatchenkia orientalis. Even in fermenting S. cerevisiae that is net releasing ethanol, media C-ethanol rapidly enters and is oxidized to acetaldehyde and acetyl-CoA. This is evident in exogenous ethanol being a major source of both cytosolic and mitochondrial acetyl units. H-tracing reveals that ethanol is also a major source of both NADH and NADPH high-energy electrons, and this role is augmented under oxidative stress conditions. Thus, uncoupling of glycolysis from the oxidation of glucose-derived carbon via rapidly reversible reactions is a conserved feature of eukaryotic metabolism. Keywords Animals, Glucose, Citric Acid Cycle, Lactates, Mammals, Saccharomyces cerevisiae, Fermentation, Ethanol Journal Nat Chem Biol Volume 18 Issue 12 Pages 1380-1387 Date Published 2022 Dec ISSN Number 1552-4469 DOI 10.1038/s41589-022-01091-7 Alternate Journal Nat Chem Biol PMCID 1082793 PMID 35970997 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML