Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose:: A simple analysis by 13C NMR of urinary menthol glucuronide
Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose:: A simple analysis by 13C NMR of urinary menthol glucuronide
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DOI：
10.1002/mrm.21057
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发表时间：
2006-11-01
影响因子：
3.3
通讯作者：
Jones, John G.
中科院分区：
文献类型：
--
作者：
Mendes, Ana C.;Caldeira, M. Madalena;Jones, John G.
从一名体重70 kg的健康女性受试者摄入400 mg薄荷油和6 g 99% [U-C-13]葡萄糖后的尿液中分离出薄荷糖醛酸内酯。葡糖苷酸C-13过量富集水平为4-6%，因此提供了高信噪比（SNR），可通过C-13 NMR确定每个C-13共振内的C-13-C-13自旋偶联多重峰组分。通过[U-C-13]葡萄糖直接途径转化为[U-C-13] UDP-葡萄糖得到的[U-C-13]葡糖苷酸同位素异构体与[1，2，3-C-13（3）]-分离，而[1，2-C-13（2）]葡糖苷酸是通过[U-C-13]葡萄糖的科里循环或间接途径代谢得到的拓扑异构体。在第二项研究中，对一组4名夜间禁食的重度心力衰竭患者（63 +/- 10 kg）给予薄荷油并输注[U-C-13]葡萄糖4小时（14 mg/kg预充，0.12 mg/kg/min恒定输注），导致稳态血浆[U-C-13]葡萄糖富集为4.6% +/-0.6%。收获薄荷糖葡糖苷酸，并通过C-13 NMR分析葡糖苷酸C-13同位素异构体。[U-C-13]葡糖苷酸富集为0.6% +/-0.1%，[1，2，3-C-13（3）]和[1，2-C-13（2）]葡糖苷酸富集之和为0.9% +/-0.2%。根据这些数据，估计血浆葡萄糖至肝脏UDPG的通量为内源性葡萄糖产生（EGP）的15% ± 4%，并且科里循环占GP的至少32% ± 10%。
Menthol glucuronlide was isolated from the urine of a healthy-70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-C-13]glucose. Glucuronide C-13-excess enrichment levels were 4-6% and thus provided high signa to-noise ratios (SNRs) for confident assignment of C-13-C-13 Spin-coupled multiplet components within each C-13 resonance by C-13 NMR. The [U-C-13]glucuronide isotopomer derived via dire pathway conversion of [U-C-13]glucose to [U-C-13] UDP-glucose was resolved from [1,2,3-C-13(3)]- and [1,2-C-13(2)]glucuronide is topomers derived via Cori cycle or indirect pathway metabolism of [U-C-13]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were give peppermint oil and infused with [U-C-13]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-C-13]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide C-13-isotopomers were analyzed by C-13 NMR. [U-C-13]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-C-13(3)] an [1,2-C-13(2)]glucuronide enrichments was 0.9% +/- 0.2%. Fro these data, flux of plasma glucose to hepatic UDPG was est mated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.