Tracing tracers

When tracing tracers, researchers have the opportunity to study kinetic aspects of metabolism in vivo. Stable isotope-labeled metabolites, or tracers, are administered to subjects according to carefully designed protocols, and their occurrence in thoughtfully chosen sample matrices is analyzed, either in unchanged or metabolized form. This enables assessment of kinetic features of metabolism, and tracing of the fate of the compounds under normal conditions, in disease, or following an intervention. The applications of tracer protocols are numerous, and countless opportunities for new studies involving tracers lie ahead. The use of stable isotope-labeled tracers is safe and, depending on the specific research question, the protocols of administration and sampling can be very patient-friendly. Tracer studies provide a unique insight into metabolism and give access to kinetic information of in vivo processes, that cannot be obtained in any other way.
This thesis features both technical aspects of tracer methods (Part I) and clinical applications of tracer techniques (Part II). The development and validation of sensitive and accurate analysis methods for metabolites involved in glyoxylate metabolism, octanoate, and sugars, and application of these methods to samples obtained during tracer protocols were described. We developed and executed clinical tracer protocols to investigate basic aspects of metabolism, or to compare responses to dietary interventions or new medicine. The majority of the research presented in this thesis involved inborn errors of metabolism.