Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells

• Published in: Developmental cell Vol. 36; no. 5; pp. 540 - 549
• Main Authors: Hosios, Aaron M., Hecht, Vivian C., Danai, Laura V., Johnson, Marc O., Rathmell, Jeffrey C., Steinhauser, Matthew L., Manalis, Scott R., Vander Heiden, Matthew G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.03.2016
• Subjects: Amino Acids - metabolism; Animals; Carbon - metabolism; Cell Proliferation - physiology; Cells, Cultured; Citric Acid Cycle - physiology; Glucose - metabolism; Glutamic Acid - metabolism; Glutamine - metabolism; Humans
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2016.02.012

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and found that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, suggesting that glutamine's ability to replenish tricarboxylic acid cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis. [Display omitted] •Glucose and glutamine are not the sources of the majority of mammalian cell mass•Non-glutamine amino acids provide abundant carbon and nitrogen to proliferating cells•Non-proliferating mammalian cells exhibit variable degrees of cell mass turnover•Nutrient fates are determined, showing that glutamine contributes primarily to protein Hosios et al. analyze nutrient contributors to cell mass and find that although glucose and glutamine have the highest consumption rates, the majority of proliferative cell mass actually derives from non-glutamine amino acids. This quantitative analysis provides a framework for understanding proliferative metabolism of mammalian cells and cancer metabolism.