Work

Dependence of Mouse Embryonic Stem Cells on Threonine Catabolism

Year: 2009

Type: article

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.

Source: Science

DOI: 10.1126/science.1173288

Authors: Jian Wang, Peter Alexander, Leeju Wu, Robert Hammer, Ondine Cleaver, Steven L. McKnight

Institution: The University of Texas Southwestern Medical Center

Language: English

Topic: Amino Acid Enzymes and Metabolism

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of Diabetes and Digestive and Kidney Diseases

Award: Endothelial Signals During Organogenesis