Lactate is always the end product of glycolysis

Matthew J. Rogatzki, Brian S. Ferguson, Matthew L. Goodwin, L. Bruce Gladden

Research output: Contribution to journalArticlepeer-review

159 Scopus citations


Through much of the history of metabolism, lactate (La-) has been considered merely a dead-end waste product during periods of dysoxia. Congruently, the end product of glycolysis has been viewed dichotomously: pyruvate in the presence of adequate oxygenation, La- in the absence of adequate oxygenation. In contrast, given the near-equilibrium nature of the lactate dehydrogenase (LDH) reaction and that LDH has a much higher activity than the putative regulatory enzymes of the glycolytic and oxidative pathways, we contend that La- is always the end product of glycolysis. Cellular La- accumulation, as opposed to flux, is dependent on (1) the rate of glycolysis, (2) oxidative enzyme activity, (3) cellular O2 level, and (4) the net rate of La- transport into (influx) or out of (efflux) the cell. For intracellular metabolism, we reintroduce the Cytosol-to-Mitochondria Lactate Shuttle. Our proposition, analogous to the phosphocreatine shuttle, purports that pyruvate, NAD++, NADH, and La- are held uniformly near equilibrium throughout the cell cytosol due to the high activity of LDH. La- is always the end product of glycolysis and represents the primary diffusing species capable of spatially linking glycolysis to oxidative phosphorylation.

Original languageEnglish
Article number22
JournalFrontiers in Neuroscience
Issue numberFEB
StatePublished - 2015


  • Aerobic
  • Anaerobic
  • Cytosolic lactate shuttle
  • Lactate dehydrogenase
  • Mitochondria
  • NADH
  • Pyruvate


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