Use of Stable Isotopes to Assess Protein and Amino Acid Metabolism in Children and Adolescents: A Brief Review

Abstract

As protein accretion is a prerequisite for growth, studying the mechanisms by which nutrients and hormones promote protein gain is of the utmost relevance to paediatric endocrinology. Tracers are ideally suited for the assessment of protein and amino acid kinetics in vivo, as they provide an estimate of synthesis and turnover. Current tracer approaches in children and adolescents utilize stable isotopes, ‘heavier’ forms of elements that have one or several extra neutrons in the nucleus. Such isotopes are already present at low, but significant, levels in all tissues and foodstuffs, are not radioactive and are devoid of any known side-effects when present in small amounts. L-[1-¹³C] labelled leucine, given as a 4- to 6-h intravenous infusion, has become the method of choice to assess whole-body protein kinetics. After infusion, any ¹³C-leucinethat is oxidized appears in the breath as ¹³CO₂, whereas the remainder is incorporated into body proteins through protein synthesis. The isotope enrichments are determined by isotope ratio mass spectrometry and gas chromatography mass spectrometry, and absolute rates of whole-body protein synthesis, oxidation, and breakdown can be extrapolated. This approach has been used extensively to investigate the regulation of protein kinetics by nutrients and by hormones. Attempts have also been made to measure amino acid/protein metabolism in selected body compartments, and to measure the kinetics of specific tissue proteins, for example, muscle, gut, or plasma proteins.