Metabolism of Glutamine, Citrulline, and Arginine; Stable Isotopes Analyzing the Intestinal–Renal Axis

Glutamine, citrulline, and arginine are amino acids that are essential for recovery after surgery and during critical illness. Conversion of glutamine into citrulline and arginine is thought to take place within the intestinal–renal axis. The application of stable isotope amino acid tracers is essential to study metabolism at the whole-body and interorgan levels. The aim of this chapter is to summarize the use of stable isotopes to study the metabolic route of glutamine into citrulline and arginine, as an application of stable isotope methodology to nutritional metabolic research. The liquid chromatography-mass spectrometry (LC–MS) method is currently the established technique for measuring enrichments of glutamine, citrulline, and arginine with stable isotope tracers. We discuss the mass spectrometry method and review the pitfalls of the applied techniques. In the investigation of amino acid metabolism, the equations for the determination of the precursor–product relationship rely on the ratio between the enrichment of the product (derived from the precursor) and the enrichment of the precursor, which is provided as a stable isotope tracer and represents the conversion of unlabeled amino acids. Investigation of the complex pathway between glutamine, citrulline, and arginine may eventually guide the development of tailor-made nutrition for specific patient populations, with the ultimate purpose of improving outcomes.