The present article is a review written at a level suitable for students and new workers to the field of techniques in common current use for the measurement of static and dynamic features of metabolism, especially nutritional metabolism. It covers the nature of radioactive and stable-isotope tracers, the means of measuring them, and the advantages and disadvantages of their use. The greater part of the review deals with methods for the measurement of pool sizes and metabolic processes, with the emphasis being on protein metabolism, a field the author knows best. The examples given are from a variety of sources, including the work of the author, but the principles underlying the techniques are universally applicable to all metabolic investigations using tracers.

The present review discusses the advantages and limitations of using stable-isotope tracers to assess carbohydrate and fat metabolism at the whole-body level. One advantage of stable-(v. radioactive-) isotope tracers is the relative ease with which the location of a label within a molecule can be determined using selected-ion-monitoring GC-mass spectrometry (SIM-GC- MS). This technique minimizes potential problems due to label recycling, allows the use of multiple-labelled compounds simultaneously (e.g. to quantify glucose cycling), and perhaps most importantly, has led to the development of unique stable-isotope methods for, for example, quantifying gluconeogenesis. However, the limited sensitivity of SIM-GC-MS sometimes requires that relatively large amounts of a stable-isotope tracer be used, thus increasing cost and potentially altering metabolism. At least theoretically, stable- (or radioactive-) isotope tracers can also be used in conjunction with indirect calorimetry to estimate utilization of muscle glycogen or triacylglycerol stores, thus potentially circumventing the need to obtain muscle biopsies. These calculations, however, require certain critical assumptions, which if incorrect could lead to major errors in the values obtained. Despite such limitations, stable-isotope tracers provide a powerful and sometimes unique tool for investigating carbohydrate and fat metabolism at the whole-body level. With continuing advances in availability, instrumentation and methods, it is likely that stable-isotope tracers will become increasingly important in the immediate future.

The present lecture begins with a brief overview of the professional and scientific journey taken by Rudolf Schoenheimer, before turning to a discussion of the power of isotopic tracers in nutrition research. Schoenheimer's remarkable contributions to the study of intermediary metabolism and the turnover of body constituents, based initially on compounds tagged with 2H and later with 15N, spanned a mere decade. It is difficult, however, to overestimate the enormous impact of Schoenheimer's research on the evolution of biological science. After a relative hiatus, following Schoenheimer's death in 1941, in the use of stable nuclides as tracers in metabolism and nutrition, especially in human subjects, there is now an expanded and exciting range of techniques, experimental protocols and stable-isotope tracer compounds that are helping to probe the dynamic aspects of the metabolism of the major energy-yielding substrates, amino acids and other N-containing compounds, vitamins and mineral elements in human subjects. Various aspects of the contemporary applications of these tracers in nutrition research are covered in the present lecture.