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

被引:479
作者
Hosios, Aaron M. [1 ,2 ]
Hecht, Vivian C. [1 ,3 ]
Danai, Laura V. [1 ,2 ]
Johnson, Marc O. [4 ]
Rathmell, Jeffrey C. [4 ]
Steinhauser, Matthew L. [5 ,6 ,7 ]
Manalis, Scott R. [1 ,3 ]
Vander Heiden, Matthew G. [1 ,2 ,8 ]
机构
[1] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] MIT, Dept Biol Engn, Cambridge, MA 02139 USA
[4] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA
[5] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA
[6] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Boston, MA 02115 USA
[8] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
关键词
AEROBIC GLYCOLYSIS; ASPARTATE TRANSPORTER; GLUTAMINE-METABOLISM; TRANSFORMED-CELLS; CANCER METABOLISM; EPITHELIAL-CELLS; PYRUVATE-KINASE; SUPPORTS GROWTH; HUMAN-BLOOD; ACETATE;
D O I
10.1016/j.devcel.2016.02.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:540 / 549
页数:10
相关论文
共 62 条
[11]   Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells [J].
Commisso, Cosimo ;
Davidson, Shawn M. ;
Soydaner-Azeloglu, Rengin G. ;
Parker, Seth J. ;
Kamphorst, Jurre J. ;
Hackett, Sean ;
Grabocka, Elda ;
Nofal, Michel ;
Drebin, Jeffrey A. ;
Thompson, Craig B. ;
Rabinowitz, Joshua D. ;
Metallo, Christian M. ;
Vander Heiden, Matthew G. ;
Bar-Sagi, Dafna .
NATURE, 2013, 497 (7451) :633-+
[12]  
Davidson SM., 2016, Cell Metab
[13]   Metabolic reprogramming in cancer: Unraveling the role of glutamine in tumorigenesis [J].
Daye, Dania ;
Wellen, Kathryn E. .
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2012, 23 (04) :362-369
[14]   The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation [J].
DeBerardinis, Ralph J. ;
Lum, Julian J. ;
Hatzivassiliou, Georgia ;
Thompson, Craig B. .
CELL METABOLISM, 2008, 7 (01) :11-20
[15]   Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis [J].
DeBerardinis, Ralph J. ;
Mancuso, Anthony ;
Daikhin, Evgueni ;
Nissim, Ilana ;
Yudkoff, Marc ;
Wehrli, Suzanne ;
Thompson, Craig B. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (49) :19345-19350
[16]  
Dolfi SC, 2013, CANCER METAB, V1, DOI 10.1186/2049-3002-1-20
[17]  
EAGLE H, 1956, J BIOL CHEM, V218, P607
[18]   AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo [J].
Faubert, Brandon ;
Boily, Gino ;
Izreig, Said ;
Griss, Takla ;
Samborska, Bozena ;
Dong, Zhifeng ;
Dupuy, Fanny ;
Chambers, Christopher ;
Fuerth, Benjamin J. ;
Viollet, Benoit ;
Mamer, Orval A. ;
Avizonis, Daina ;
DeBerardinis, Ralph J. ;
Siegel, Peter M. ;
Jones, Russell G. .
CELL METABOLISM, 2013, 17 (01) :113-124
[19]   Why do cancers have high aerobic glycolysis? [J].
Gatenby, RA ;
Gillies, RJ .
NATURE REVIEWS CANCER, 2004, 4 (11) :891-899
[20]   Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation [J].
Heiden, Matthew G. Vander ;
Cantley, Lewis C. ;
Thompson, Craig B. .
SCIENCE, 2009, 324 (5930) :1029-1033