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  • Title: Magnetic susceptibility to measure total protein concentration from NMR metabolite spectra: Demonstration on blood plasma.
    Author: Jupin M, Michiels PJ, Girard FC, Wijmenga SS.
    Journal: Magn Reson Med; 2015 Feb; 73(2):459-68. PubMed ID: 24639074.
    Abstract:
    PURPOSE: Accurate metabolite and protein quantification in blood plasma and other body fluids from one single NMR measurement, allowing for improved quantitative metabolic profiling and better assessment of metabolite-protein interactions. THEORY AND METHODS: The total protein concentration is derived from the common chemical-shift changes-caused by protein-induced bulk magnetic susceptibility (BMS)-measured on well-accessible and exchange-free metabolite resonances. These BMS shifts are simply obtained by external referencing with respect to 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid, sodium salt in a coaxial insert. RESULTS: Based on blood-plasma data from five volunteers, the estimated accuracy of the BMS method is ≤ 5% with respect and comparable to the 3.8% error of the standard colorimetric, Biuret, method. Valine, alanine, glucose, leucine, and lactate display no exchange-induced shift changes. Their well-accessible signals act as reliable probes for pure protein-induced BMS. The slopes and intercepts of their chemical-shift change versus protein concentration were derived from metabolite mixtures with (fatted) human and bovine albumin acting as blood-plasma mimics. CONCLUSION: The BMS method, demonstrated on blood plasma, can also be used on other samples containing sufficient protein (> 10 g/L). Also, it allows measurement of the presence and sign of exchange-induced chemical-shift changes.
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