Speaker: Professor Karsten Hiller, Director of the department of Bioinformatics and Biochemistry at the University of Braunschweig, Germany, will present a seminar entitled:

Stable-isotope assisted metabolomics for Defining the Dietary Landscape

Host: Maria Traka

Abstract:

Uptake and metabolism of food is a highly complex process and requires the coordinated interaction of cells, tissues and organs in multi-cellular organisms to establish homeostasis. Already minor off-tunes in this interaction can cause disease or malfunction of the whole organism. On the other hand, the organism has to be prepared to act on various fuel types and thus to convert various types of nutrients into energy and biomass as well as building up a storage pool for times of fasting. To ensure the immediate and stable availability of energy even under high load conditions where complete carbohydrate oxidation is too slow or even not possible, the body must ensure that production and clearance of metabolites such as glucose, lactic acid or alanine are balanced. In humans and other mammals, the Cori cycle is a metabolic pathway that ensures glucose homeostasis and involves the concerted action of central organs. It recycles alanine or lactic acid produced by glucose consuming tissues back to glucose. Stable-isotope labeling is a safe procedure to profile the dynamics of metabolite turnover on a whole organism scale. Here, we present time-resolved dynamics of glucose metabolism in blood after oral administration of 13C stable-isotope labeled glucose in human subjects. We developed a protocol to extract polar metabolites from dried blood spots and apply GC/MS to acquire MS data. Time-resolved isotopic enrichment patterns (Mass Isotopomer Distributions / MIDS) in combination with absolute concentrations of the target metabolites both obtained from DBS sampling and GC/MS measurement are used as input for a mathematical ODE model. By solving the equation system of this model, we could determine quantitative and robust values for glucose production (GP) and gluconeogenesis (GNG) for each studied subject. While already providing exact and quantitative metabolic turn-over rates for metabolites directly involved in glucose metabolism such a “small system” does not highlight other parts of whole body homeostasis as for example metabolism of amino acids. To address this limitation, we are extending our focus and include quantitative flux data for more metabolites. For that purpose, we follow the fate of fully 13C labeled wheat flour after ingestion by human individuals. Due to the fact that all carbon atoms in this wheat are substituted by 13C isotopes, every wheat molecule has an increased molecular mass. The major components of wheat flour are starch and protein and the digestion and metabolism of these bio-polymers can be traced by determining isotopic enrichment patterns in plasma metabolites.

All staff from organisations on the Norwich Research Park are welcome to attend.