Amino acids rather than glucose account for the majority of cell mass in proliferating mammalian cells
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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.
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20-30% of glucose-derived 14C ends up in protein and a similar amount in RNA and DNA in cultured H1299, A549, and A172 cancer cells.
“Moreover, the group of the cancer metabolism researcher Matt Vander Heiden has demonstrated that 20–30% of glucose-derived 14C ends up in protein and a similar amount of 14C in RNA and DNA in cultured H1299, A549, and A172 cancer cells [180].”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [180]
The Results (page unavailable) report that a quarter of glucose carbon was traced to RNA and DNA, and that glucose-derived carbon was recovered in macromolecular fractions from H1299, A549, and A172 cells. They describe substantial recovery across the fractions but do not give a 20–30% figure for protein in the available text, so that numerical part is not verified. (LLM, conf=0.85)
Experimental — accuracy not yet measuredGlutamine is an important nitrogen donor for amino acids and nucleotides, but glutamine uptake can exceed the nitrogen requirement of some cancer cells.
“Glutamine is an important nitrogen donor for amino acids and nucleotides (Hosios et al., 2016), but glutamine uptake can exceed the nitrogen requirement of some cancer cells (DeBerardinis et al., 2007).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Hosios et al., 2016
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Disruption of Amino Acid Homeostasis by Novel ASCT2 Inhibitors Involves Multiple Targets
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Extracellular serine controls epidermal stem cell fate and tumour initiation
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Cancer-associated adipocytes as immunomodulators in cancer
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Drilling for Oil: Tumor-Surrounding Adipocytes Fueling Cancer
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“Moreover, the group of the cancer metabolism researcher Matt Vander Heiden has demonstrated that 20–30% of glucose-derived 14 C ends up in protein and a similar amount of 14 C in RNA and DNA in cultured H1299, A549, and A172 cancer cells [180].”
- Authors
- Hosios, A. M., Hecht, V. C., Danai, L. V., Johnson, M. O., Rathmell, J. C., Steinhauser, M. L., Manalis, S. R., & Vander Heiden, M. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Vanderbilt University Medical Center (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 36
- Issue
- 5
- Pages
- 540-549
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC4766004
- OpenAlex
- W2294143173
- Cited by
- 641
- References
- 64
- Citations by year
- 2026: 37 · 2025: 57 · 2024: 68 · 2023: 57 · 2022: 76 · 2021: 71 · 2020: 95 · 2019: 62 · 2018: 54 · 2017: 44 · 2016: 19 · 2014: 1
- FWCI
- 24.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- NIH (U54CA121852, R01CA168653, P30CA14051, R01HL108006, U54CA143874, K08DK090147)
- Burroughs Wellcome Fund
- Ludwig Center
- Damon Runyon Cancer Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- cell mass, amino acids, glucose, glutamine, cell proliferation, nutrient consumption, anaplerosis, TCA cycle, amino acid biosynthesis, protein synthesis, mammalian cells
- MeSH terms
- Amino Acids, Animals, Carbon, Cells, Cultured, Citric Acid Cycle, Glucose, Glutamine, Humans, Glutamic Acid, Cell Proliferation
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