Analytical Core

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ABSTRACT: Core C: Analytical & Metabolomic The Case MMPC specializes in the use of stable isotopes, mass spectrometry and metabolomics to investigate the regulation of pathways of intermediary metabolism in vivo and ex vivo. Emphasis is on quantitative measurements of inter-organ and intra-organ carbon fluxes. Our strategy links clinical-type studies (limited to body fluids) and pure biochemical studies (such as the kinetics of purified enzymes). The association of metabolomics and mass isotopomer analysis provides a wealth of information on the regulation of known pathways. It also allows to identify new pathways. Metabolomics developed initially as a non-targeted strategy aimed at gathering sufficient data on a (patho)physiological process (biomarkers), so that one could formulate hypotheses to be tested. A variant of this strategy is to target metabolomic studies to classes of compounds, the concentrations and labeling patterns of which can provide much new information: citric acid cycle intermediates, (hydroxy)acids, acyl-CoA esters, acylcarnitine esters. The Case MMPC occupies a specialized niche in the MMPC consortium, complementing the expertise of the other centers, but with a healthy degree of overlap with the Vanderbiit, Yale, Dallas and Cincinnati centers. The specific aims of the Analytical & Metabolomic Core are: 1. To help users in the design, implementation, analytical procedures and interpretation of metabolic studies conducted either, (i) entirely in the user's lab, (ii) entirely in the Case MMPC, or (iii) partly in the user's lab (animal experiments) and partly in the MMPC (analyses of tissues and body fluids shipped from the user's lab). 2. To set up, at users' request, tests and analytical procedures not currently listed on the web page of the Case MMPC. 3. To develop analytical techniques and isotopic strategies in anticipation of users' needs. 4. To train US and foreign scientists in the proper use of isotopes for metabolic studies. This training takes to form of (i) mentoring individual users, and (ii) contribution to an annual MMPC course.