Arteriovenous Blood Metabolomics: A Readout of Intra-Tissue Metabostasis.
Arteriovenous Blood Metabolomics: A Readout of Intra-Tissue Metabostasis.
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DOI：
10.1038/srep12757
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发表时间：
2015-08-05
影响因子：
4.6
通讯作者：
Siuzdak G
中科院分区：
文献类型：
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作者：
Ivanisevic J;Elias D;Deguchi H;Averell PM;Kurczy M;Johnson CH;Tautenhahn R;Zhu Z;Watrous J;Jain M;Griffin J;Patti GJ;Siuzdak G
人体循环系统由动脉血和静脉血组成，动脉血向组织输送营养物质，静脉血清除代谢副产物。尽管动脉血的葡萄糖和氧浓度通常高于静脉血，但尚未报道动静脉差异的全面生化表征。在这里，我们应用尖端的，基于质谱的代谢组学技术，以提供一个全球性的特征的代谢物，在人类患者的动脉和静脉血之间的浓度变化。对来自20名健康个体的成对动脉和静脉血浆进行全局分析，随后进行靶向分析，使得有可能测量水溶性人血浆代谢物组中细微（<2倍）但高度统计学显著和生理学重要的差异。虽然我们检测到乳酸、丙氨酸、谷氨酰胺和谷氨酸的变化，正如骨骼肌活动所预期的那样，但也确定了许多非预期的代谢物发生了显著改变，包括克雷布斯循环中间体、先前未参与转运的氨基酸和一些氧化脂肪酸。这项研究提供了迄今为止最全面的评估血液循环过程中的代谢变化，并表明这种分析方法可能会提供新的见解器官稳态和器官特异性病理学。
The human circulatory system consists of arterial blood that delivers nutrients to tissues, and venous blood that removes the metabolic by-products. Although it is well established that arterial blood generally has higher concentrations of glucose and oxygen relative to venous blood, a comprehensive biochemical characterization of arteriovenous differences has not yet been reported. Here we apply cutting-edge, mass spectrometry-based metabolomic technologies to provide a global characterization of metabolites that vary in concentration between the arterial and venous blood of human patients. Global profiling of paired arterial and venous plasma from 20 healthy individuals, followed up by targeted analysis made it possible to measure subtle (<2 fold), yet highly statistically significant and physiologically important differences in water soluble human plasma metabolome. While we detected changes in lactic acid, alanine, glutamine, and glutamate as expected from skeletal muscle activity, a number of unanticipated metabolites were also determined to be significantly altered including Krebs cycle intermediates, amino acids that have not been previously implicated in transport, and a few oxidized fatty acids. This study provides the most comprehensive assessment of metabolic changes in the blood during circulation to date and suggests that such profiling approach may offer new insights into organ homeostasis and organ specific pathology.