核磁共振波谱法发现人血清中大量谷氨酰胺环化为焦谷氨酸,Analytical Chemistry

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核磁共振波谱法发现人血清中大量谷氨酰胺环化为焦谷氨酸
Analytical Chemistry ( IF 6.7 ) Pub Date : 2015-03-17 00:00:00 , DOI: 10.1021/ac504435b
G. A. Nagana Gowda , Yashas N. Gowda , Daniel Raftery ₁

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谷氨酰胺是血液中最丰富的代谢产物之一，是许多重要代谢途径的中心，也是其前体和终产物。谷氨酰胺的许多令人惊讶和出乎意料的作用，包括最近发现的癌细胞谷氨酰胺成瘾，都强调了准确分析谷氨酰胺浓度对于了解其在健康和许多疾病中的作用的重要性。利用最近开发的NMR方法，该方法可获取前所未有的可量化血液代谢产物，我们已经发现了在蛋白质去除过程中谷氨酰胺环化成焦谷氨酸的过程令人惊讶。使用¹对来自同一人血清的完整，超滤和蛋白质沉淀样品进行了全面研究在800 MHz处进行1 H NMR光谱检测和定量评估该现象。有趣的是，尽管谷氨酰胺环化发生在超滤和蛋白沉淀的血清中，但在完整血清中未检测到环化。令人惊讶的是，由于环化作用，表观血清谷氨酰胺水平下降了多达75％，随之而来的焦谷氨酸水平也成比例地增加。此外，实际上在相同的条件下，来自同一组人血清的样品的不同部分的环化程度差异很大。但是，每个样品中谷氨酰胺和焦谷氨酸的浓度总和对于所有部分都相同。这些出乎意料的发现表明，考虑从现代分析方法获得的表观谷氨酰胺和焦谷氨酸含量之和的重要性，

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Massive Glutamine Cyclization to Pyroglutamic Acid in Human Serum Discovered Using NMR Spectroscopy

Glutamine is one of the most abundant metabolites in blood and is a precursor as well as end product central to numerous important metabolic pathways. A number of surprising and unexpected roles for glutamine, including cancer cell glutamine addiction discovered recently, stress the importance of accurate analysis of glutamine concentrations for understanding its role in health and numerous diseases. Utilizing a recently developed NMR approach that offers access to an unprecedented number of quantifiable blood metabolites, we have identified a surprising glutamine cyclization to pyroglutamic acid that occurs during protein removal. Intact, ultrafiltered and protein precipitated samples from the same pool of human serum were comprehensively investigated using ¹H NMR spectroscopy at 800 MHz to detect and quantitatively evaluate the phenomenon. Interestingly, although glutamine cyclization occurs in both ultrafiltered and protein precipitated serum, the cyclization was not detected in intact serum. Strikingly, due to cyclization, the apparent serum glutamine level drops by up to 75% and, concomitantly, the pyroglutamic acid level increases proportionately. Further, virtually under identical conditions, the magnitude of cyclization is vastly different for different portions of samples from the same pool of human serum. However, the sum of glutamine and pyroglutamic acid concentrations in each sample remains the same for all portions. These unexpected findings indicate the importance of considering the sum of apparent glutamine and pyroglutamic acid levels, obtained from the contemporary analytical methods, as the actual blood glutamine level for biomarker discovery and biological interpretations.

更新日期：2015-03-17

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