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Dependence of mouse embryonic stem cells on threonine catabolism.


ABSTRACT: 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.

SUBMITTER: Wang J 

PROVIDER: S-EPMC4373593 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Dependence of mouse embryonic stem cells on threonine catabolism.

Wang Jian J   Alexander Peter P   Wu Leeju L   Hammer Robert R   Cleaver Ondine O   McKnight Steven L SL  

Science (New York, N.Y.) 20090709 5939


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 tr  ...[more]

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