Large deuterium isotope effects and their use: a historical review.

Isotope effects are differences in the properties of the isotopes of an element resulting in different reaction rates of a corresponding compound, in equilibrium constants and in the spectra. Shortly after the discovery of stable isotopes of hydrogen, oxygen, and carbon, Jacob Bigeleisen formulated a theory of isotope effects and calculated possible maximum values. Large isotope effects of (2)H (deuterium) against (1)H (protium) were seen to possibly influence interpretations of reaction mechanisms if corresponding labelling is used. Much work was invested to ensure the safety of deuterium use in men in spite of the large isotope effect. On the other hand, large deuterium isotope effects gave rise to several practical applications. Examples are the enhancement of the stability of some technical products against oxidative and against hydrolytic degradation (oils, pharmaceuticals) as well as alterations of the detoxification metabolism of pharmaceuticals in vivo.

The Rudolf Schoenheimer Centenary Lecture. Isotopes in nutrition research.

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.

The history and theory of the doubly labeled water technique.

Scientists have been measuring energy expenditure by using gas exchange for the past 200 y. This technique is based on earlier work in the 1660s. Gas exchange in respirometers provides accurate and repeatable measures of resting metabolic rate. However, it is impossible to duplicate in a respirometry chamber the diversity of human behaviors that influence energy expenditure. The doubly labeled water technique is an isotope-based method that measures the energy expenditure of unencumbered subjects from the divergence in enrichments of 2 isotopic labels in body water--1 of hydrogen and 1 of oxygen. The method was invented in the 1950s and applied to small animals only until the early 1980s, mostly because of the expense. Since 1982, when the first study in humans was published, its use has expanded enormously. Although there is some debate over the precise calculation protocols that should be used, the differences between alternative calculations result in relatively minor effects on total energy expenditure estimates (approximately 6%). Validation studies show that for groups of subjects the method works well, but that precision is still relatively poor (8-9%) and consequently the method is not yet sufficiently refined to provide estimates of individual energy expenditures.