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来自[U-¹³C]葡萄糖的肝脏UDP-葡萄糖¹³C同位素异构体:通过¹³C NMR对尿中薄荷醇葡萄糖醛酸苷进行的简单分析

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

作者信息

Mendes Ana C, Caldeira M Madalena, Silva Claudia, Burgess Shawn C, Merritt Matthew E, Gomes Filipe, Barosa Cristina, Delgado Teresa C, Franco Fatima, Monteiro Pedro, Providencia Luis, Jones John G

机构信息

Department of Chemistry, University of Coimbra, Coimbra, Portugal.

出版信息

Magn Reson Med. 2006 Nov;56(5):1121-5. doi: 10.1002/mrm.21057.

DOI:10.1002/mrm.21057
PMID:17036288
Abstract

Menthol glucuronide 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-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.

摘要

在一名体重70千克的健康女性受试者摄入400毫克薄荷油和6克99%的[U-(13)C]葡萄糖后,从其尿液中分离出了薄荷醇葡萄糖醛酸苷。葡萄糖醛酸苷的(13)C过量富集水平为4% - 6%,因此通过(13)C NMR为每个(13)C共振内的(13)C-(13)C自旋耦合多重峰成分的可靠归属提供了高信噪比(SNR)。通过[U-(13)C]葡萄糖直接途径转化为[U-(13)C]UDP-葡萄糖衍生的[U-(13)C]葡萄糖醛酸苷异构体与通过科里循环或[U-(13)C]葡萄糖间接途径代谢衍生的[1,2,3-(13)C(3)]-和[1,2-(13)C(2)]葡萄糖醛酸苷异构体得以区分。在第二项研究中,一组四名隔夜禁食的重度心力衰竭患者(63±10千克)服用了薄荷油,并输注[U-(13)C]葡萄糖4小时(初始剂量14毫克/千克,持续输注速率0.12毫克/千克/分钟),导致稳态血浆[U-(13)C]葡萄糖富集为4.6%±0.6%。收集了薄荷醇葡萄糖醛酸苷,并通过(13)C NMR分析葡萄糖醛酸苷的(13)C异构体。[U-(13)C]葡萄糖醛酸苷富集为0.6%±0.1%,[1,2,3-(13)C(3)]和[1,2-(13)C(2)]葡萄糖醛酸苷富集之和为0.9%±0.2%。根据这些数据,估计血浆葡萄糖向肝UDPG的通量为内源性葡萄糖生成(EGP)的15%±4%,科里循环至少占葡萄糖生成(GP)的32%±10%。

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