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

115 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 (US)
Article number22
JournalFrontiers in Neuroscience
Issue numberFEB
StatePublished - 2015
Externally publishedYes


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

ASJC Scopus subject areas

  • Neuroscience(all)


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