Quantitative NMR-Based Biomedical Metabolomics: Current Status and Applications

Abstract

Nuclear Magnetic Resonance (NMR) spectroscopy is a quantitative analytical tool commonly utilized for metabolomics analysis. Quantitative NMR (qNMR) is a field of NMR spectroscopy dedicated to the measurement of analytes through signal intensity and its linear relationship with analyte concentration. Metabolomics-based NMR exploits this quantitative relationship to identify and measure biomarkers within complex biological samples such as serum, plasma, and urine. In this review of quantitative NMR-based metabolomics, the advancements and limitations of current techniques for metabolite quantification will be evaluated as well as the applications of qNMR in biomedical metabolomics. While qNMR is limited by sensitivity and dynamic range, the simple method development, minimal sample derivatization, and the simultaneous qualitative and quantitative information provide a unique landscape for biomedical metabolomics, which is not available to other techniques. Furthermore, the non-destructive nature of NMR-based metabolomics allows for multidimensional analysis of biomarkers that facilitates unambiguous assignment and quantification of metabolites in complex biofluids.

Advances and Perspectives in Prostate Cancer Biomarker Discovery in the Last 5 Years through Tissue and Urine Metabolomics

“…Currently, the majority of the metabolic studies are performed using mass spectrometry (MS), frequently coupled with a separation technique like gas or liquid chromatography (GC–MS or LC–MS), and nuclear magnetic resonance spectroscopy (NMR) [ 26 , 29 ]. MS and NMR show several differences, including in the detected range of concentrations, namely, MS allows the detection of metabolites in concentrations ranging from picomolar (pM) to millimolar (mM) [ 30 ] and NMR from micromolar (µM) to millimolar (mM) [ 31 ]. Table 1 summarizes the advantages and limitations of the three analytical techniques (GC–MS, LC–MS and NMR), for metabolomic studies.…”

Biomarker Discovery in Atherosclerotic Diseases Using Quantitative Nuclear Magnetic Resonance Metabolomics

“…According to the size of the particle, the lipid methyl and methylene moieties in lipoproteins resonate at different frequencies, with smaller particles resonating at lower frequencies. Therefore, the concentrations of lipoproteins can be quantitated when decomposing the methyl and methylene signals of the core lipids into individual signals or using statistical methods to estimate the entire envelope ( 64 ).…”

Automatic 1D 1H NMR Metabolite Quantification for Bioreactor Monitoring

“…Most existing quantitative NMR literature focus on biofluids that are relevant for clinical applications of NMR metabolomics. Many such applications have test samples that arise from controlled environments, which are similar to the standards from public libraries [ 9 , 21 , 22 ]. Conversely, bioreactors, generally defined as vessels where biological reaction or change is taking place, can involve enzymes (e.g., for cell-free bioprocessing), microorganisms (e.g., for environmental remediation or fermentation), animal cells (e.g., for production of biologics or vaccines), plant cells (e.g., for production of bioactive compounds), and tissues (e.g., for cell therapies).…”

“…There are a few recent reviews that touch on quantitative NMR (e.g., [ 9 , 21 , 22 ]). However, to the best of our knowledge, benchmark or performance analysis for existing quantitative NMR approaches applied to the bioreactor setting is lacking.…”