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The metabolism of cell growth: aerobic glycolysis
Author(s) -
Thompson Craig B.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a45
Subject(s) - extracellular , microbiology and biotechnology , metabolism , glycolysis , biology , autophagy , anaerobic glycolysis , bioenergetics , nutrient sensing , intracellular , biochemistry , receptor , cell , metabolic pathway , carbohydrate metabolism , cell metabolism , signal transduction , mitochondrion , apoptosis
Past metabolic studies have focused on terminally differentiated cells. These studies suggested that cells maintain bioenergetics through cell‐autonomous uptake of available extracellular nutrients, including glucose, lipids, and amino acids, and feeding the catabolites of these nutrients into the TCA cycle. Recent studies in several mammalian cell types have led us to reconsider whether nutrient uptake is in fact cell‐autonomous. When cultured in the absence of extracellular ligands that direct nutrient uptake, mammalian cells lack the ability to take up sufficient nutrients to sustain ATP synthesis. Under these conditions, cells must depend on autophagy to supply bioenergetic substrates that are derived primarily from cellular lipids. Although autophagy can sustain a cell for several weeks, it is ultimately a self‐limited survival strategy. Cellular dependence on receptor‐directed extracellular ligand‐directed nutrient uptake establishes a mechanism by which all cells in multicellular organisms might be rendered dependent on extracellular ligands for survival. This model also suggests all cells express receptors that can initiate signal transduction events directing the cell to take up nutrients in a manner analogous to the way insulin directs glucose uptake in insulin‐responsive tissues. In the cells examined to date, lineage‐specific receptors have been identified which, when maximally stimulated, can direct the cell to take up glucose in excess of its needs. This results in the conversion of intermediate metabolism to a form of aerobic glycolysis (the Warburg Effect). The net effects of this metabolism are a diversion of available amino acids into protein synthesis and the establishment of an alternative mitochondrial/cytoplasmic citric acid cycle that converts glucose into lipids. The glucose taken up in excess of the cell's ability to process it through these alternative pathways is metabolized to lactate and secreted. This receptor‐directed transition to aerobic glycolysis defines a previously unappreciated form of intermediate metabolism that is adaptive to the support of cell growth.