Wang Jian, Alexander Peter, Wu Leeju, Hammer Robert, Cleaver Ondine, McKnight Steven L
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.
Science. 2009 Jul 24;325(5939):435-9. doi: 10.1126/science.1173288. Epub 2009 Jul 9.
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.
对培养的胚胎干细胞（ES细胞）中常见代谢物丰度的测量揭示了其一碳代谢的异常状态。这些发现导致了ES细胞中编码苏氨酸脱氢酶（TDH）的基因大量表达的发现。TDH介导的苏氨酸分解代谢在线粒体中发生，生成甘氨酸和乙酰辅酶A（CoA），其中甘氨酸通过甘氨酸裂解系统促进一碳代谢，而乙酰辅酶A进入三羧酸循环。分别去除20种氨基酸中的每一种的培养基应用于ES细胞，从而发现ES细胞严重依赖一种氨基酸——苏氨酸。这些观察结果表明，ES细胞存在于与快速生长的细菌细胞相当的高通量主干代谢状态中。
