Metabolism plays a central role in cancer progression. Rewiring glucose metabolism is essential for fulfilling the high energy and biosynthetic demands as well as for the development of drug resistance. Nevertheless, the role of other diet-abundant natural sugars is not fully understood. In this study, we performed a comprehensive 2D NMR spectroscopy tracer-based assay with a panel of13C-labelled sugars (glucose, fructose, galactose, mannose and xylose). We assigned over 100 NMR signals from metabolites derived from each sugar and mapped them to metabolic pathways, uncovering two novel findings. First, we demonstrated that mannose has a semi-identical metabolic profile to that of glucose with similar label incorporation patterns. Second, next to the known role of fructose in driving one-carbon metabolism, we explained the equally important contribution of galactose to this pathway. Interestingly, we demonstrated that cells growing with either fructose or galactose became less sensitive to certain one-carbon metabolism inhibitors such as 5-Flurouracil and SHIN1. In summary, this study presents the differential metabolism of natural sugars, demonstrating that mannose has a comparable profile to that of glucose. Conversely, galactose and fructose contribute to a greater extent to one-carbon metabolism, which makes them important modulators for inhibitors targeting this pathway. To our knowledge, this is the first NMR study to comprehensively investigate the metabolism of key natural sugars in AML and cancer.
代谢在癌症进展中扮演核心角色。葡萄糖代谢的重编程对于满足高能量和生物合成需求以及耐药性的发展至关重要。然而，其他饮食中丰富的天然糖类的作用尚未被完全理解。在本研究中，我们采用了一套13C标记糖（葡萄糖、果糖、半乳糖、甘露糖和木糖）进行了全面的二维核磁共振光谱示踪分析。我们鉴定了来自每种糖的代谢物中超过100个核磁共振信号，并将它们映射到代谢途径中，揭示了两项新发现。首先，我们证明甘露糖具有与葡萄糖相似的代谢谱，标记掺入模式也类似。其次，除了已知果糖在驱动一碳代谢中的作用外，我们解释了半乳糖对该途径同样重要的贡献。有趣的是，我们发现使用果糖或半乳糖生长的细胞对某些一碳代谢抑制剂（如5-氟尿嘧啶和SHIN1）的敏感性降低。总之，本研究展示了天然糖类的差异代谢，证明甘露糖具有与葡萄糖相当的代谢谱。相反，半乳糖和果糖在一碳代谢中贡献更大，这使它们成为针对该途径抑制剂的重要调节因子。据我们所知，这是首次利用核磁共振技术全面研究急性髓系白血病及癌症中关键天然糖类代谢的研究。
肿瘤(癌症)患者之家