Isotopes in nutrition research

Abstract

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.

Tracking the Oxidative and Nonoxidative Fates of Isotopically Labeled Nutrients in Animals

“…The dominance of radioisotopes in metabolic and nutrition research continued through the 1970s, when stable isotopes began to supplant their use (Young and Ajami 1999). This shift was primarily driven by changing public awareness about the safety of radioisotopes, technological advances in mass spectrometry, and reduced costs of labeled tracers (Young and Ajami 1999); however, several other advantages of stable isotopes over radioisotopes are often cited: (a) Stable isotopes pose no significant health risks at tracer concentrations, (b) stable isotopes do not degrade over time and thus permit longterm experiments, (c) stable isotope tracers and tissue samples can be stored for extended periods, (d) several different stable isotope nuclides can be administered simultaneously, (e) stable isotope studies do not require approval by the Atomic Energy Commission, and (f) there are no special requirements for disposing of stable isotope waste.…”

“…The amount of "C in solid, liquid, and gaseous samples can be quantified using various mass spectrometric approaches (see reviews in Turnlund 1989, Bier 1997, Rennie 1999, Young and Ajami 1999. Gas chromatography-isotope ratio mass spectrometry (GC-IRMS) is one of the most popular approaches, and 2).…”

Hitler's Gift and the Era of Biosynthesis

“…Valuable accounts of Schoenheimer's career have been published by Kohler (12) and by Young and Ajami (13). He was born in Berlin in 1898 (12).…”

Metabolism 2000: the emperor needs new clothes

“…This same enzyme takes on a 'moonlighting' role in biopterin cofactor regeneration, as stated earlier (p. 36), and therefore also becomes an important counter-regulatory effector for NO synthesis. Similarly, the normal role of CD26 is to serve as a T-helper 1 cell activation antigen and signal-binding site, while in its 'moonlighting' capacity as dipeptidyl peptidase IV it hydrolyzes chemokines and regulatory peptides, such as RANTES (regulated on activation, normal T-cell expressed and secreted) and glucagon-like peptide 1 respectively (Young & Ajami, 1999b). Function depends on whether the protein (enzyme) appears to act in its normal role or 'moonlighting' role and the 'moonlighting' aspects can be particularly instructive in understanding the natural history of pathophysiologies, which otherwise cannot be predicted by genomic potential alone.…”