Lower glycolysis involves a series of reversible reactions, which interconvert intermediates that also feed anabolic pathways. 3-phosphoglycerate (3-PG) is an abundant lower glycolytic intermediate that feeds serine biosynthesis via the enzyme phosphoglycerate dehydrogenase, which is genomically amplified in several cancers. Phosphoglycerate mutase 1 (PGAM1) catalyzes the isomerization of 3-PG into the downstream glycolytic intermediate 2-phosphoglycerate (2-PG). PGAM1 needs to be histidine phosphorylated to become catalytically active. We show that the primary PGAM1 histidine phosphate donor is 2,3-bisphosphoglycerate (2,3-BPG), which is made from the glycolytic intermediate 1,3-bisphosphoglycerate (1,3-BPG) by bisphosphoglycerate mutase (BPGM). When BPGM is knocked out, 1,3-BPG can directly phosphorylate PGAM1. In this case, PGAM1 phosphorylation and activity are decreased, but nevertheless sufficient to maintain normal glycolytic flux and cellular growth rate. 3-PG, however, accumulates, leading to increased serine synthesis. Thus, one biological function of BPGM is controlling glycolytic intermediate levels and thereby serine biosynthetic flux.

中文翻译：

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Bisphosphoglycerate突变酶通过3-phosphoglycerate控制丝氨酸途径通量

低级糖酵解涉及一系列可逆反应，这些反应可相互转化中间体，这些中间体也可提供合成代谢途径。3-磷酸​​甘油酸（3-PG）是一种丰富的低级糖酵解中间体，可通过磷酸甘油酸脱氢酶来提供丝氨酸的生物合成，该酶在一些癌症中被基因组扩增。磷酸甘油酸突变酶1（PGAM1）催化3-PG异构化为下游糖酵解中间体2-磷酸甘油酸（2-PG）。PGAM1需要被组氨酸磷酸化才能具有催化活性。我们显示主要的PGAM1组氨酸磷酸供体是2,3-双磷酸甘油酸酯（2,3-BPG），它是由双磷酸甘油酸突变酶（BPGM）由糖酵解中间体1,3-双磷酸甘油酸酯（1,3-BPG）制成的。当BPGM被敲除时，1,3-BPG可以直接磷酸化PGAM1。在这种情况下，PGAM1的磷酸化和活性降低，但是仍然足以维持正常的糖酵解通量和细胞生长速率。然而，3-PG积累，导致丝氨酸合成增加。因此，BPGM的一种生物学功能是控制糖酵解中间水平，从而控制丝氨酸生物合成通量。