Dependence of mouse embryonic stem cells on threonine catabolism.
Measurements of the abundance of common metabolites in cultured embryonic stem (ES) cells revealed an unusual state with respect to one-carbon metabolism. These findings led to the discovery of copious expression of the gene encoding threonine dehydrogenase (TDH) in ES cells. TDH-mediated catabolism of threonine takes place in mitochondria to generate glycine and acetyl-coenzyme A (CoA), with glycine facilitating one-carbon metabolism via the glycine cleavage system and acetyl-CoA feeding the tricarboxylic acid cycle. Culture media individually deprived of each of the 20 amino acids were applied to ES cells, leading to the discovery that ES cells are critically dependent on one amino acid--threonine. These observations show that ES cells exist in a high-flux backbone metabolic state comparable to that of rapidly growing bacterial cells.
Wang
Jian
J
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.
Alexander
Peter
P
Wu
Leeju
L
Hammer
Robert
R
Cleaver
Ondine
O
McKnight
Steven L
SL
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D013912:Threonine / Q000378:metabolism*; D046509:Tissue Culture Techniques
D003470:Culture Media; D013912:Threonine; D000429:Alcohol Oxidoreductases; C023159:L-threonine 3-dehydrogenase