An introduction to biological nuclear magnetic resonance spectroscopy

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful analytical techniques available to biology. This review is an introduction to the potential of this method and is aimed at readers who have little or no experience in acquiring or analyzing NMR spectra. We focus on spectroscopic applications of the magnetic resonance effect, rather than imaging ones, and explain how various aspects of the NMR phenomenon make it a versatile tool with which to address a number of biological problems. Using detailed examples, we discuss the use of (1) H NMR spectroscopy in mixture analysis and metabolomics, the use of (13) C NMR spectroscopy in tracking isotopomers and determining the flux through metabolic pathways ('fluxomics') and the use of (31) P NMR spectroscopy in monitoring ATP generation and intracellular pH homeotasis in vivo. Further examples demonstrate how NMR spectroscopy can be used to probe the physical environment of a cell by measuring diffusion and the tumbling rates of individual metabolites and how it can determine macromolecular structures by measuring the bonds and distances which separate individual atoms. We finish by outlining some of the key challenges which remain in NMR spectroscopy and we highlight how recent advances-such as increased magnet field strengths, cryogenic cooling, microprobes and hyperpolarisation-are opening new avenues for today's biological NMR spectroscopists.

The Path to Personalized Cardiovascular Medicine

“…Two core technologies-mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy-are at the heart of modern sensitive proteomic and metabolomic analyses (see also Chapter 2). [254][255][256][257][258][259][260][261][262][263] Typical ultrasensitive MS-based proteomics workflow includes extensive sample prefractionation, digestion of proteins, high performance liquid chromatography (HPLC) of generated peptides with subsequent electrospray ionization, MS analysis and identification of peptide sequences, protein identification and quantification through database searching (Figure 24.7).…”

Renal bioenergetics during early gram-negative mammalian sepsis and angiotensin II infusion

“…Such techniques introduce powerful confounds, including the effect of abdominal surgery, organ manipulation and organ injury, especially in small animals. In contrast, MR spectroscopy is recognized as a highly accurate, widely validated analytical tool that represents the gold standard for the non-invasive measurement of ATP and intracellular pH [25][26][27], and importantly can be performed repeatedly to study the evolution of changes in ATP during sepsis. Such multiple non-invasive measurements carry greater statistical and pathophysiological robustness and less confounding influences.…”

Metabolomics in Cardiovascular Disease: Towards Clinical Application

“…A more detailed description of the applications of biological NMR spectroscopy can be found elsewhere [Bothwell and Griffin 2011] When sample classification, as in the case of disease diagnosis, is the primary objective, metabonomics or metabolic fingerprinting is the desired approach. In this case, NMR spectroscopy is the preferred analytical technique because it is fast, reproducible and cheap on a per-sample basis.…”