Lactate: the ugly duckling of energy metabolism.

Nature Metabolism
Joshua D Rabinowitz, Sven Enerbäck

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.

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Citations

Sep 22, 2020·American Journal of Physiology. Endocrinology and Metabolism·Lawrence Kazak, Bruce M Spiegelman
Jan 21, 2021·Cell Metabolism·Tara TeSlaaJoshua D Rabinowitz
Oct 23, 2020·International Journal of Molecular Sciences·Xavier Remesar, Marià Alemany
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Mar 5, 2021·Pharmacology & Therapeutics·Lingfan LiangZeping Hu
Feb 26, 2021·Nature Reviews. Endocrinology·Pauline MorignyDominique Langin
Feb 11, 2021·Angewandte Chemie·Yongwoo JangSeon Jeong Kim
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Mar 20, 2021·Biotechnology and Bioengineering·Corinna SchmidtAline Zimmer
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