NMR Laboratory, Center for Neurosciences and Cell Biology, Coimbra University, Coimbra, Portugal.
Magn Reson Med. 2009 Nov;62(5):1120-8. doi: 10.1002/mrm.22107.
Sources of hepatic glycogen synthesis during an oral glucose tolerance test were evaluated in six healthy subjects by enrichment of a 75-g glucose load with 6.67% [U-(13)C]glucose and 3.33% [U-(2)H(7)]glucose and analysis of plasma glucose and hepatic uridine diphosphate-glucose enrichments (sampled as urinary menthol glucuronide) by (2)H and (13)C nuclear magnetic resonance. The direct pathway contribution, as estimated from the dilution of [U-(13)C]glucose between plasma glucose and glucuronide, was unexpectedly low (36 +/- 5%). With [U-(2)H(7)]glucose, direct pathway estimates based on the dilution of position 3 (2)H-enrichment between plasma glucose and glucuronide were significantly higher (51 +/- 6%, P = 0.05). These differences reflect the exchange of the carbon 4, 5, and 6 moiety of fructose-6-phosphate and glyceraldehyde-3-phosphate catalyzed by transaldolase. As further evidence of this exchange, (2)H-enrichments in glucuronide positions 4 and 5 were inferior to those of position 3. From the difference in glucuronide positions 5 and 3 enrichments, the fraction of direct pathway carbons that experienced transaldolase exchange was estimated at 21 +/- 4%. In conclusion, the direct pathway contributes only half of hepatic glycogen synthesis during an oral glucose tolerance test. Glucose tracers labeled in positions 4, 5, or 6 will give significant underestimates of direct pathway activity because of transaldolase exchange.
在六位健康受试者中，通过将 75g 葡萄糖负荷用 6.67%[U-(13)C]葡萄糖和 3.33%[U-(2)H(7)]葡萄糖进行富集，并通过(2)H 和(13)C 核磁共振分析血浆葡萄糖和肝尿苷二磷酸葡萄糖的富集（作为尿薄荷基葡萄糖醛酸苷进行采样），评估口服糖耐量试验期间肝糖原合成的来源。直接途径的贡献，根据血浆葡萄糖和葡萄糖醛酸之间[U-(13)C]葡萄糖的稀释来估计，出乎意料地低（36 +/- 5%）。用[U-(2)H(7)]葡萄糖，基于血浆葡萄糖和葡萄糖醛酸之间位置 3（2）H 富集稀释的直接途径估计值明显更高（51 +/- 6%，P = 0.05）。这些差异反映了转醛醇酶催化的果糖-6-磷酸和甘油醛-3-磷酸的碳 4、5 和 6 部分的交换。作为这种交换的进一步证据，葡萄糖醛酸位置 4 和 5 的（2）H 富集低于位置 3。根据葡萄糖醛酸位置 5 和 3 的富集差异，经历转醛醇酶交换的直接途径碳的分数估计为 21 +/- 4%。总之，在口服糖耐量试验期间，直接途径仅贡献肝糖原合成的一半。由于转醛醇酶交换，在位置 4、5 或 6 标记的葡萄糖示踪剂将显著低估直接途径的活性。
