Research Article

Dependence of Mouse Embryonic Stem Cells on Threonine Catabolism

Science  24 Jul 2009:
Vol. 325, Issue 5939, pp. 435-439
DOI: 10.1126/science.1173288

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Threonine Required

Embryonic stem (ES) cells divide rapidly, raising the possibility that they might exist in a metabolic state that facilitates rapid growth. By monitoring the abundance of common metabolites in mouse ES cells, Wang et al. (p. 435; published online 9 July) found altered levels of metabolites involved in carbon metabolism. Measurement of messenger RNA levels revealed unusually high expression of the gene encoding threonine dehydrogenase. In addition, in growth experiments, mouse ES cells were critically dependent on the amino acid threonine.

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.

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