Principles of stable isotope research – with special reference to protein metabolism

Daniel J Wilkinson,Matthew S Brook,Ken Smith

doi:10.1016/j.nutos.2021.02.005

Daniel J Wilkinson, Matthew S Brook + Show 1 more

Open Access

https://doi.org/10.1016/j.nutos.2021.02.005

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Abstract

SummaryThe key to understanding the mechanisms regulating disease stems from the ability to accurately quantify the dynamic nature of the metabolism underlying the physiological and pathological changes occurring as a result of the disease. Stable isotope tracer technologies have been at the forefront of this for almost 80 years now, and through a combination of both intense theoretical and technological development over these decades, it is now possible to utilise stable isotope tracers to investigate the complexities of in vivo human metabolism from a whole body perspective, down to the regulation of sub-nanometer cellular components (i.e organelles, nucleotides and individual proteins). This review therefore aims to highlight; 1) the advances made in these stable isotope tracer approaches – with special reference given to their role in understanding the nutritional regulation of protein metabolism, 2) some considerations required for the appropriate application of these stable isotope techniques to study protein metabolism, 3) and finally how new stable isotopes approaches and instrument/technical developments will help to deliver greater clinical insight in the near future.

Highlights

The key to understanding the mechanisms regulating disease stems from the ability to accurately quantify the dynamic nature of the metabolism underlying the physiological and pathological changes occurring as a result of the disease
Stable isotope tracer technologies have been at the forefront of this for almost 80 years and through a combination of both intense theoretical and technological development over these decades, it is possible to utilise stable isotope tracers to investigate the complexities of in vivo human metabolism from a whole body perspective, down to the regulation of sub-nanometer cellular components (i.e organelles, nucleotides and individual proteins)
This review aims to highlight; 1) the advances made in these stable isotope tracer approaches e with special reference given to their role in understanding the nutritional regulation of protein metabolism, 2) some considerations required for the appropriate application of these stable isotope techniques to study protein metabolism, 3) and how new stable isotopes approaches

Summary

A brief history of stable isotope tracers e from deuterium and back again

Stable isotopes have helped shape our understanding of human physiology, metabolism and disease for almost a century and it is the unique properties of stable isotopes that have enabled such progress. Schoenheimer and Rittenberg were able to rapidly (producing 14 papers on the topic in only a few years; [1]) uncover previously unknown facets involved in the regulation of mammalian metabolism; and by the end of the 1930s, with the identification and incorporation of the stable isotopes of carbon (13C; [4]), nitrogen (15N; [5,6]) and oxygen Despite these exciting early developments, the expected expansion in the use of these metabolic tools was somewhat delayed by around 40 years, due in part to the discovery and utilisation of the easier, yet potentially more hazardous, radiolabelled isotopes and the lack of access to the appropriate analytical technology i.e. mass spectrometers, with the required sensitivity to analyse stable isotope tracers [10]. Technical application of stable isotopes to protein metabolic research; from whole body to single tissue

Whole body protein metabolism measures using stable isotope tracers

Methodological developments and future applications

Findings

AA stimulate MPS