Massive glutamine cyclization to pyroglutamic acid in human serum discovered using NMR spectroscopy

Analytical Chemistry
G A Nagana GowdaDaniel Raftery

Abstract

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 (1)H 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 cyclizati...Continue Reading

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Citations

Sep 1, 2016·Current Opinion in Biotechnology·John L MarkleyDavid S Wishart
Mar 16, 2017·Journal of Proteome Research·Jens WallmeierUNKNOWN GCKD Study Investigators
Jul 30, 2017·Clinical Endocrinology·Chen-Tian ShenQuan-Yong Luo
Dec 18, 2018·PLoS Neglected Tropical Diseases·Caitlin D FrenchCarolyn M Slupsky
Oct 20, 2017·Metabolomics : Official Journal of the Metabolomic Society·Irina M VelskoChristina Warinner
Dec 18, 2019·Organic & Biomolecular Chemistry·Sergio Di SilvioGennaro Pescitelli
Oct 15, 2018·Journal of Bioscience and Bioengineering·Hiromi Miyagawa, Takeshi Bamba
Jan 3, 2018·Analytical Chemistry·G A Nagana GowdaDaniel Raftery

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