Mini-symposium on NMR-based metabolic fingerprinting and profiling

2nd April 2008 at 9:15 in the Benzon Auditorium

The Faculty of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen

The symposium is a Drug Research Academy, PHARMA event organized by J. W. Jaroszewski (jj(at)farma.ku.dk), C. Cornett, N. Nyberg and D. Stærk, Faculty of Pharmaceutcal Sciences, University of Copenhagen.

The participation is free of charge and is open for attendance by all interested parties. No prior registration is required.

Lipoprotein and metabolite analytics by 1H NMR spectroscopy of serum: Implications for metabolic phenotyping for disease risk assessment

Mika Ala-Korpela

Computational Medicine Research Group;Helsinki University of Technology, Faculty of Information and Natural Sciences, Department of Biomedical Engineering and Computational Science & Folkhälsan Research Center, Institute of Genetics, Department of Diabetes Genetics, FinnDiane Study Group & Helsinki University Central Hospital, Department of Medicine, Division of Nephrology, Helsinki, Finland

Abstract

The non-selective nature along with metabolic specificity and various molecular windows available are advantageous characteristics of 1H NMR spectroscopy in metabonomics [1]. Recent results will be presented on the inherent suitability of ¹H NMR spectroscopy to identify subtle changes in lipoprotein subclass-related metabolism together with several other metabolites of high interest in clinical medicine. Based on a single ¹H NMR protocol, we have developed a new framework to visualise and interpret the data and to link the multi-metabolic phenotypes to the underlying diagnostic and biochemical variables [2]. Our work emphasises the diffuse nature of complex vascular diseases and the fundamental limitations of a single-biomarker approach. However, it also promises cost-effective clinical solutions via high-throughput analytics and advanced computational methods. Our studies indicate the importance of combining the macromolecular information with data from low-molecular-weight metabolites in serum for disease risk assessment and diagnostics. We also discuss how our application of ¹H NMR metabonomics and statistical visualisations may improve the tracking of patients’ progress in the diabetic disease continuum in a way not attainable by traditional approaches. Hence, it may become possible to re-route the multimetabolite path of a vulnerable patient away from adverse clinical endpoints and towards a more favourable phenotype before it is too late.

[1] Ala-Korpela M. Expert Rev Mol Diagn. 2007;7:761.
[2] Mäkinen VP, Soininen P, Forsblom C, Parkkonen M, Ingman P, Kaski K,
      Groop PH, Ala-Korpela M. Mol Syst Biol. 2008;4:167.

Applications of NMR-based metabonomics

Henrik Toft

Protein Structure and Biophysics, Protein Engineering
Novo Nordisk Park, 2760 Måløv

Abstract

Metabonomics studies of pharmaceutical relevance generally use bio-fluids, or cell or tissue extracts. Urine and plasma are easily obtained, essentially non-invasively, and hence can be readily used for disease diagnosis and in a clinical trials setting for monitoring drug therapy. However other body fluids as well as faeces and tissue biopsies without extraction can be analysed. For fluids analysis can be carried out in tubes or via a flow injection system, whereas solids such as e.g. a muscle biopsy must be analysed by Magic Angle Spinning (MAS). This presentation will show examples of actual application of NMR-based metabonomics in both in vitro cell assays and in vivo animal model studies as well as human clinical investigations. All of the presented data have been acquired at Novo Nordisk.

NMR-based metabolomics of plants

Christoph Seger

Institute of Pharmacy, University of Innsbruck, Josef-Moeller-Haus, Innrain 52, A-6020 Innsbruck

Abstract

Systems biology can be considered as one of the most important novel concepts in natural sciences. Based on the tremendous achievements in different –omics fields as genomics, proteomics, and metabonomics, a novel understanding of the complexity of interactions within a living organism emerged. The information flow from DNA over proteins to metabolites yields a vast array of secondary natural products of astonishing structural variety. These are – in contrast to „primary metabolites“ – produced by adaptive complex metabolic pathways biogenetically well separated from the uniform, conserved and universal primary life function sustaining mechanisms. Analytical technologies allowing the systematic qualitative and quantitative analysis of both primary and secondary metabolites have been associated with buzz words like metabonomics, metabolomics, metabolic profiling or metabolic fingerprinting. This lecture will be devoted to discuss the differences between these approaches. Based on an analysis of a metabolite profiling workflow, the limitations of realizing such projects on instrumental analysis platforms as GC-MS, HPLC-MS and NMR will be illustrated. A special emphasis will be given on the technical realization of the combined use of NMR spectroscopy and multivariate data analysis for metabolic profiling. This technology has been proven especially promising if secondary natural product profiles have to be analyzed as application examples from our laboratory and from the literature will demonstrate.