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

Clin Nutr Open Sci. 2021 Apr:36:111-125. doi: 10.1016/j.nutos.2021.02.005.

Abstract

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 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.

Keywords: A-V, Arterial Venous; AA, Amino Acids; AP(E), Atom percent (excess); FBR, Fractional Breakdown Rate; FSR, Fractional Synthesis Rate; GC-MS, Gas Chromatography Mass Spectrometry; LC-MS, Liquid Chromatography Mass Spectrometry; MPS, Muscle Protein Synthesis; Muscle; Protein turnover; Ra, Rate of Appearance; Rd, Rate of Disappearance; Stable isotope tracers.