Submitted on March 9, 2009
Accepted on June 17, 2009
Dependence of Mouse Embryonic Stem Cells on Threonine Catabolism
Jian Wang 1, Peter Alexander 1, Leeju Wu 1, Robert Hammer 1, Ondine Cleaver 2, Steven L. McKnight 1*
1 Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390–9152, USA.
2 Department of Molecular Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390–9152, USA.
* To whom correspondence should be addressed.
Steven L. McKnight , E-mail: Steven.McKnight{at}UTSouthwestern.edu
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-CoA, with glycine facilitating one-carbon metabolism via the glycine cleavage system and acetyl-CoA feeding the tricarboxcylic acid (TCA) 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 upon but one amino acid—threonine. These observations show that ES cells exist in a unique, high-flux backbone metabolic state comparable to that of rapidly growing bacterial cells.
