Control, bioenergetics, and adaptation in health and disease: noninvasive biochemistry from nuclear magnetic resonance

The noninvasive study of cellular homeostasis, control, and energetics in tissues and organs within intact living systems is now possible. Nuclear magnetic resonance (NMR) spectroscopy in vivo provides information about key metabolites, reaction rates, the control of ionic equilibria and fluxes (including that of H+), and molecular diffusion and motions within the cell. When phosphorus (31P) is measured, the processes associated with the production and utilization of adenosine triphosphate (ATP) are followed. Using 13C for measurement, the pathways and fluxes in the synthesis and degradation of sugars (e.g., glycogen), amino acids, etc., can be observed. Intracellular, cytoplasmic pH (H+ concentration) can be determined from the 31P-NMR spectrum of organs and cells whereas Na+ and K+ (or its congener Rb+) are directly measurable by NMR. All these can be observed in physiological situations in almost any organism in the animal or plant kingdom. The bioenergetics of locust muscle in flight is as readily measured as that in human muscle in health, training, and disease. When spatially resolved, the NMR spectra can provide metabolic maps of the human heart, brain, and other organs. Thus we can now directly delineate the biochemical basis of human diseases.