Guanosine diphosphate mannose (GDP-Man) is the donor substrate required for mannosylation in the synthesis of glycoproteins, glycolipids and the newly discovered glycoRNA. Normal GDP-Man biosynthesis plays a crucial role in support of a variety of cellular functions, including cell recognition, cell communication and immune responses against viruses. Here, we report the detection of GDP-Man in human brain for the first time, using ³¹P MRS at 7 T. The presence of GDP-Man is evidenced by the detection of a weak ³¹P doublet at −10.7 ppm that can be assigned to the phosphomannosyl group (Pβ) of the GDP-Man molecule. This weak but well-resolved signal lies 0.9 ppm upfield of UDP(G) Pβ-multiplet from a mixture of UDP-Glc, UDP-Gal, UDP-GlcNAc and UDP-GalNAc. In reference to ATP (2.8 mM), the concentration of GDP-Man in human brain was estimated to be 0.02 ± 0.01 mM, about 15-fold lower than the total concentration of UDP(G) (0.30 ± 0.04, N = 17) and consistent with previous reports of UDP-Man in cells and brain tissue extracts measured by high-performance liquid chromatography. The reproducibility of the measured GDP-Man between test and 2-week retest was 21% ± 15% compared with 5% ± 4% for UDP(G) (N = 7). The measured concentrations of GDP-Man and UDP(G) are linearly correlated ([UDP(G)] = 4.3 [GDP-Man] + 0.02, with R = 0.66 and p = 0.0043), likely reflecting the effect of shared sugar precursors, which may vary among individuals in response to variation in nutritional intake and consumption. Given that GDP-Man has another set of doublet (Pα) at −8.3 ppm that overlaps with NAD(H) and UDP(G)-Pα signals, the amount of GDP-Man could potentially interfere with the deconvolution of these mixed signals in composition analysis. Importantly, this new finding may be useful in advancing our understanding of glycosylation and its role in the development of cancer, as well as infectious and neurodegenerative diseases.

中文翻译：

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健康人脑的 31P-MRS：7 T 时鸟苷二磷酸甘露糖的测量

鸟苷二磷酸甘露糖 (GDP-Man) 是糖蛋白、糖脂和新发现的糖 RNA 合成中甘露糖基化所需的供体底物。正常的 GDP-Man 生物合成在支持多种细胞功能方面发挥着至关重要的作用，包括细胞识别、细胞通讯和针对病毒的免疫反应。在这里，我们首次报告了在 7 T 下使用³¹ P MRS 在人脑中检测到 GDP-Man。GDP-Man 的存在通过检测到弱³¹-10.7 ppm 的 P 双峰可归属于 GDP-Man 分子的磷酸甘露糖基 (Pβ)。这种微弱但解析良好的信号位于来自 UDP-Glc、UDP-Gal、UDP-GlcNAc 和 UDP-GalNAc 混合物的 UDP(G) Pβ-multiplet 的 0.9 ppm 高场。参考 ATP (2.8 mM)，估计人脑中 GDP-Man 的浓度为 0.02 ± 0.01 mM，比 UDP(G) (0.30 ± 0.04, N = 17) 的总浓度低约 15 倍并且与通过高效液相色谱法测量的细胞和脑组织提取物中的 UDP-Man 的先前报道一致。在测试和 2 周重新测试之间测量的 GDP-Man 的可重复性为 21% ± 15%，而 UDP(G) (N = 7) 为 5% ± 4%。GDP-Man 和 UDP(G) 的测量浓度呈线性相关 ([UDP(G)] = 4.3 [GDP-Man] + 0.02，R = 0.66 和p = 0.0043），可能反映了共享糖前体的影响，这可能因个体之间的营养摄入和消耗的变化而有所不同。鉴于 GDP-Man 在 -8.3 ppm 处具有另一组与 NAD(H) 和 UDP(G)-Pα 信号重叠的双峰 (Pα)，GDP-Man 的量可能会干扰这些混合信号的反卷积成分分析。重要的是，这一新发现可能有助于促进我们对糖基化及其在癌症、传染病和神经退行性疾病发展中的作用的理解。