Abstract

The human body is in a constant state of turnover, that is, being synthesized, broken down and/or converted to different compounds. The dynamic nature of in vivo kinetics of human metabolism at rest and in stressed conditions such as exercise and pathophysiological conditions such as diabetes and cancer can be quantitatively assessed with stable, nonradioactive isotope tracers in conjunction with gas or liquid chromatography mass spectrometry and modeling. Although measurements of metabolite concentrations have been useful as general indicators of one's health status, critical information on in vivo kinetics of metabolites such as rates of production, appearance or disappearance of metabolites are not provided. Over the past decades, stable, nonradioactive isotope tracers have been used to provide information on dynamics of specific metabolites. Stable isotope tracers can be used in conjunction with molecular and cellular biology tools, thereby providing an in-depth dynamic assessment of metabolic changes, as well as simultaneous investigation of the molecular basis for the observed kinetic responses. In this review, we will introduce basic principles of stable isotope methodology for tracing in vivo kinetics of human or animal metabolism with examples of quantifying certain aspects of in vivo kinetics of carbohydrate, lipid and protein metabolism.

Highlights

  • The human body is in a dynamic homeostasis

  • The muscle protein pool size in the body is relatively constant in healthy adults because the continual breakdown of muscle protein is matched by a corresponding synthesis of new muscle protein

  • A change in pool size reflects either net synthesis, that is, synthesis exceeding breakdown or net breakdown, that is, breakdown exceeding synthesis. This dynamic nature of various aspects of human metabolism can be best explored in vivo by the use of stable, nonradioactive tracers with the help of gas or liquid chromatography mass spectrometry (GC/Mass spectrometry (MS) or LC/MS)

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Summary

Introduction

The human body is in a dynamic homeostasis. In other words, all aspects of the body are in a state of turnover, that is, being synthesized, broken down and/or converted to different compounds. A change in pool (for example, protein) size reflects either net synthesis, that is, synthesis exceeding breakdown (for example, muscle hypertrophy) or net breakdown, that is, breakdown exceeding synthesis (for example, cancer cachexia and sarcopenia). This dynamic nature of various aspects of human metabolism can be best explored in vivo by the use of stable, nonradioactive tracers with the help of gas or liquid chromatography mass spectrometry (GC/MS or LC/MS).

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