The use of stable isotopes in metabolic investigation

The use of tracers to define substrate dynamics has been the sine qua non of metabolic investigation in vivo, because static measurements of substrate content alone are inadequate. The judicious use of radioactively labelled compounds remains the principal tracer approach in some adult subjects. However, in certain young adults, in pregnant women and in children, stable isotope tracers offer a practical alternative for answering important metabolic questions. In the last decade, the developmental problems previously associated with employing stable isotope tracers for this purpose have largely disappeared. Furthermore, the use of stable isotopically labelled materials offers certain additional advantages which are either difficult or impossible to achieve using radiotracers. These include the ability to measure simultaneously substrate content and isotopic enrichment with very high specificity and precision, the ability to determine the intramolecular location of the label, the ability to use the mass of the stable isotope substrate as a probe of the metabolite system response to perturbation, and the ability to study simultaneously and repeatedly the same subject with multiple substrate tracers. The practical application of these principles has been amply demonstrated by the expanding use of non-radioactive tracers to study body composition, energy balance, and the inter-organ transport and oxidation of the three major metabolic fuels--glucose, fat and amino acids. Continued development in the organic synthesis of new, stable isotopically labelled biochemicals will allow investigation of additional areas of biomedical importance which have been hitherto inaccessible to this approach, particularly in the pathophysiology of metabolic events in the growing child.