Lactate: the ugly duckling of energy metabolism

Joshua D. Rabinowitz, Sven Enerbäck

Research output: Contribution to journalArticle

Abstract

Lactate, perhaps the best-known metabolic waste product, was first isolated from sour milk, in which it is produced by lactobacilli. Whereas microbes also generate other fermentation products, such as ethanol or acetone, lactate dominates in mammals. Lactate production increases when the demand for ATP and oxygen exceeds supply, as occurs during intense exercise and ischaemia. The build-up of lactate in stressed muscle and ischaemic tissues has established lactate’s reputation as a deleterious waste product. In this Perspective, we summarize emerging evidence that, in mammals, lactate also serves as a major circulating carbohydrate fuel. By providing mammalian cells with both a convenient source and sink for three-carbon compounds, circulating lactate enables the uncoupling of carbohydrate-driven mitochondrial energy generation from glycolysis. Lactate and pyruvate together serve as a circulating redox buffer that equilibrates the NADH/NAD ratio across cells and tissues. This reconceptualization of lactate as a fuel—analogous to how Hans Christian Andersen’s ugly duckling is actually a beautiful swan—has the potential to reshape the field of energy metabolism.

Original languageEnglish (US)
Pages (from-to)566-571
Number of pages6
JournalNature Metabolism
Volume2
Issue number7
DOIs
StatePublished - Jul 1 2020

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Internal Medicine
  • Cell Biology

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