Biophysics and Biomedical NMR, Center for Neurosciences and Cell Biology, University of Coimbra, 3001-401 Coimbra, Portugal.
Metabolism. 2012 Feb;61(2):250-4. doi: 10.1016/j.metabol.2011.06.022. Epub 2011 Sep 8.
During feeding, dietary galactose is a potential source of hepatic glycogen synthesis; but its contribution has not been measured to date. In the presence of deuterated water ((2)H(2)O), uridine diphosphate (UDP)-glucose derived from galactose is not enriched, whereas the remainder derived from glucose-6-phosphate (G6P) is enriched in position 2 to the same level as body water, assuming complete G6P-fructose-6-phosphate (F6P) exchange. Hence, the difference between UDP-glucose position 2 and body water enrichments reflects the contribution of galactose to glycogen synthesis relative to all other sources. In study 1, G6P-F6P exchange in 6 healthy subjects was quantified by supplementing a milk-containing breakfast meal with 10 g of [U-(2)H(7)]glucose and quantifying the depletion of position 2 enrichment in urinary menthol glucuronide. In study 2, another 6 subjects ingested (2)H(2)O and acetaminophen followed by an identical breakfast meal with 10 g of [1-(13)C]glucose to resolve direct/indirect pathways and galactose contributions to glycogen synthesis. Metabolite enrichments were determined by (2)H and (13)C nuclear magnetic resonance. In study 1, G6P-F6P exchange approached completion; therefore, the difference between position 2 and body water enrichments in study 2 (0.20% ± 0.03% vs 0.27% ± 0.03%, P < .005) was attributed to galactose glycogenesis. Dietary galactose contributed 19% ± 3% to glycogen synthesis. Of the remainder, 58% ± 5% was derived from the direct pathway and 22% ± 4% via the indirect pathway. The contribution of galactose to hepatic glycogen synthesis was resolved from that of direct and indirect pathways using a combination of (2)H(2)O and [1-(13)C]glucose tracers.
在喂养过程中，膳食半乳糖是肝糖原合成的潜在来源；但迄今为止，其贡献尚未被测量。在氘水（(2)H(2)O）存在的情况下，来自半乳糖的尿苷二磷酸（UDP）-葡萄糖不会被富集，而来自葡萄糖-6-磷酸（G6P）的其余部分在位置 2 被富集到与体水相同的水平，假设 G6P-果糖-6-磷酸（F6P）完全交换。因此，UDP-葡萄糖位置 2 与体水富集之间的差异反映了半乳糖相对于其他所有来源对糖原合成的贡献。在研究 1 中，通过在含牛奶的早餐中补充 10 g [U-(2)H(7)]葡萄糖，并定量测量尿薄荷醇葡萄糖醛酸中位置 2 富集的消耗，来量化 6 名健康受试者的 G6P-F6P 交换。在研究 2 中，另外 6 名受试者摄入(2)H(2)O 和对乙酰氨基酚，然后摄入相同的含 10 g [1-(13)C]葡萄糖的早餐，以解决直接/间接途径和半乳糖对糖原合成的贡献。通过(2)H 和(13)C 核磁共振确定代谢物的富集。在研究 1 中，G6P-F6P 交换接近完成；因此，研究 2 中位置 2 和体水之间的差异（0.20%±0.03%与 0.27%±0.03%，P<0.005）归因于半乳糖糖生成。膳食半乳糖对糖原合成的贡献为 19%±3%。其余部分中，58%±5%来自直接途径，22%±4%通过间接途径。使用(2)H(2)O 和[1-(13)C]葡萄糖示踪剂的组合，解决了半乳糖对肝糖原合成的贡献与直接和间接途径的贡献。
