Monitoring Metabolism with NMR

The self-assembly of living systems is first and foremost based on structure, but function is also essential for life. At the cellular level, the function of life is founded on the ability to use energy to preserve structure: to bias the tendency to decay into the maximum probability state, the state of highest entropy. This metabolism is a yin-yang phenomenon, with catabolism tearing down our food, reducing it to simple, energy-rich molecules and anabolism using these to build up and maintain our structures. Since living systems are transparent to the radiofrequencies involved with NMR, we can use this form of spectroscopy to monitor both the anabolic and catabolic processes in what amounts to real time in living systems, without tissue damage. In the organism, metabolism occurs in every cell; the pennies of the energy economy are adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD) molecules. A typical organ, composed of many cells, is the liver in mammals, whose direct circulatory path from the gut brings it the molecules needed for life: the lipids, carbohydrates, amino acids, and nucleic acids that sustain us all. As an example of the yin-yang of metabolism, we present 13C NMR analyses of carbohydrate metabolism in the liver, including glycogenesis, glycogenolysis, and gluconeogenesis from 13C isotopically enriched substrates, as well as the synthesis of glutamate/glutamine and ketones from [3-13C]-alanine and measurements of the Red/Ox status of liver cells.