Glutamine metabolism to cancer therapy BMIT lab Adv
Glutamine metabolism to cancer therapy BMIT 김영훈 교수님 lab 손은철
Adv Physiol Educ 28: 160– 179, 2004;
Hallmarks of cancer Cell Volume 144, Issue 5, 4 March 2011, Pages 646 -674
Glutamine • Most mammalian cells in tissue culture cannot proliferate or even survive in an environment that does not contain millimolar levels of glutamine. • Glutamine is also the most abundant amino acid in the human bloodstream, 0. 5 m. M. • Glutamine accounts for about 4. 7% of all amino acid residues in human proteome. • However, consumption of glutamine in proliferatin cells far exceeds the demands imposed by protein synthesis. The EMBO Journal Vol 36 | No 10 | 2017
Glutamine as a nitrogen and carbon donor The EMBO Journal Vol 36 | No 10 | 2017
Glutamine as a nitrogen donor
Glutamine control of amino acids pool Nature review : cancer, 622 | OCTOBER 2016 | VOLUME 16
Role of glutamine in redox control The EMBO Journal Vol 36 | No 10 | 2017
Glutamine enhances GSH production Journal of parenteral and enteral nutrition, 1998, 22. 4.
Glutamine contributes to NADPH production Son et al. 2013, nature, 496, 104
Glutamine metabolism contributes to chromatin organization The EMBO Journal Vol 36 | No 10 | 2017
Glutamine as a mediator of amino acids uptake 1784 Cancer Res; 75(9) May 1, 2015
Glutamine as a mediator of m. TOR activation
Bidirectional Transport of L-Glutamine and EAA Cell Volume 136, Issue 3, 6 February 2009, Pages 521 -534
Cellular adaptations to glutamine limitation c-Myc The EMBO Journal Vol 36 | No 10 | 2017
Protein and cell corpses can supply glutamine The EMBO Journal Vol 36 | No 10 | 2017
• Glutamine as a nitrogen donor • Glutamine as a carbon donor • Glutamine as a mediator of amino acids uptake and m. TOR activation • Glutamine metabolism contributes to chromatin organization • Role of glutamine in redox control
mitochondrial aspartate export can contribute to cytosolic redox homeostasis Cell Metabolism 28, 706– 720, November 6, 2018
Knockdown of AGC 1 Reduces Proliferation Due to Impaired Aspartate Synthesis Cell Metabolism 28, 706– 720, November 6, 2018
AGC 1 -KD Increases Cellular Dependence on Glutamine Cell Metabolism 28, 706– 720, November 6, 2018
Aspartate metabolism Cell Metabolism 28, 706– 720, November 6, 2018
Cytosolic Aspartate Is Limiting for Nucleotide Biosynthesis When Glutamine Metabolism Is Compromised Cell Metabolism 28, 706– 720, November 6, 2018
Asparagine Plays a Critical Role in Regulating Cellular Adaptation to Glutamine Depletion Molecular Cell 56, 205– 218, October 23, 2014
Cystine uptake triggers cell death by cataplerosis J. Biol. Chem. (2017) 292(34) 14240– 14249
KEAP 1 -NRF 2 -x. CT axis E. Habibetal. /Redox. Biology 5(2015)33– 42
KEAP 1 mutations cause increased dependency on exogenous glutamine Sayin et al. e. Life 2017; 6: e 28083
x. CT/Slc 7 a 11 -dependent glutamate secretion in Keap 1 mutant cells causes glutamine dependency Sayin et al. e. Life 2017; 6: e 28083
x. CT/Slc 7 a 11 -dependent glutamate secretion in Keap 1 mutant cells causes glutamine dependency Sayin et al. e. Life 2017; 6: e 28083
Keap 1 mutants have defects in glutamine anaplerosis Sayin et al. e. Life 2017; 6: e 28083
KEAP 1 mutations predict sensitivity to glutaminase inhibitors across multiple cancer subtypes Sayin et al. e. Life 2017; 6: e 28083
Discussion
Nature review : cancer, 622 | OCTOBER 2016 | VOLUME 16
Cell Metabolism 7, January 2008
Int. J. Cancer: 135, 1060– 1071 (2014)
Int. J. Cancer: 135, 1060– 1071 (2014)
ASCT 2, future target of cancer therapy Nature Medicine volume 24, pages 194– 202 (2018)
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