Cellular purines, particularly adenosine 5′-triphosphate (ATP), fuel many metabolic reactions, but less is known about the direct effects of pyrimidines on cellular metabolism. We found that pyrimidines, but not purines, maintain pyruvate oxidation and the tricarboxylic citric acid (TCA) cycle by regulating pyruvate dehydrogenase (PDH) activity. PDH activity requires sufficient substrates and cofactors, including thiamine pyrophosphate (TPP). Depletion of cellular pyrimidines decreased TPP synthesis, a reaction carried out by TPP kinase 1 (TPK1), which reportedly uses ATP to phosphorylate thiamine (vitamin B1). We found that uridine 5′-triphosphate (UTP) acts as the preferred substrate for TPK1, enabling cellular TPP synthesis, PDH activity, TCA-cycle activity, lipogenesis, and adipocyte differentiation. Thus, UTP is required for vitamin B1 utilization to maintain pyruvate oxidation and lipogenesis.

中文翻译：

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嘧啶维持线粒体丙酮酸氧化以支持从头脂肪生成

细胞嘌呤，特别是 5'-三磷酸腺苷 (ATP)，为许多代谢反应提供动力，但人们对嘧啶对细胞代谢的直接影响知之甚少。我们发现嘧啶（而非嘌呤）通过调节丙酮酸脱氢酶（PDH）活性来维持丙酮酸氧化和三羧酸柠檬酸（TCA）循环。 PDH 活性需要足够的底物和辅因子，包括焦磷酸硫胺素 (TPP)。细胞嘧啶的消耗减少了 TPP 合成，这是由 TPP 激酶 1 (TPK1) 进行的反应，据报道 TPP 激酶 1 使用 ATP 磷酸化硫胺素（维生素 B1）。我们发现尿苷 5'-三磷酸 (UTP) 是 TPK1 的首选底物，促进细胞 TPP 合成、PDH 活性、TCA 循环活性、脂肪生成和脂肪细胞分化。因此，UTP 是利用维生素 B1 维持丙酮酸氧化和脂肪生成所必需的。