Nuclear Magnetic Resonance Spectroscopy Studies of Cancer Cell Metabolism

Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique that provides information on biochemical status and physiological processes both in-vitro and in-vivo. The metabolism of intact cells and tissues can be studied in a continuous manner, and thus, NMR is a unique non-invasive research tool enabling detection of the metabolic changes as they occur (Cohen et al., 1983; Morris, 1988; Daly and Cohen, 1989). The first NMR study of cellular metabolism was done some 20 years ago, when Moon and Richards reported on the diphosphoglyceric acid (DPG) and pH shifts in erythrocytes (Moon, and Richards, 1973). NMR studies of metabolism of tumor cells were initiated by Navon et al. who investigated phosphorylated compounds in Ehrlich ascites cells (Navon etal., 1977). The choice of the element and isotope for a specific study of metabolism depends on its NMR properties, and the required data. The proton has the highest NMR sensitivity, and is the most abundant nucleus in biological molecules. However, this may cause difficulties in the interpretation and assignment of the 1H NMR spectrum. Moreover, since metabolic studies are usually performed in aqueous solutions, the huge signal from the water protons should be suppressed. Similarly, the wide signals arising from proteins and membrane components should be suppressed. These problems can be addressed now by several innovative NMR methods (Daniels et al., 1976; van Zijl and Cohen, 1992). The most widely used nucleus in NMR studies of metabolism has been 31p (see reviews Cohen (1988); Kaplan et al. (1992)). Phosphorous NMR spectroscopy can provide data on energy metabolism and substrate utilization, phospholipid pathways, precise intracellular pH, and membrane permeability and ion and water distribution. The spectrum is easy to interpret, but the number of compounds which are detectable is limited. Carbon NMR is also useful for NMR studies of metabolism since it is found in most biological compounds; however, 13C has a natural abundance of only 1.1%, and 13C enrichment is necessary. Other nuclei which are used less often in NMR studies of cellular metabolism are 23Na (Gupta et al., 1984), 19F (Malet-Martino, et al., 1986), and rarely 15N (Legerton et al., 1983) and 39K (Brophy et al., 1983).