Clinical Metabolism Core

Director, Gerald I. Shulman, MD, PhD Department of Internal Medicine 300 Cedar Street P.O. Box 208020 New Haven, CT 06520-8020 USA Email: gerald.shulman@yale.edu Telephone: (203) 785-5447

Stable isotopes offer unique advantages over traditional radioisotopic methods for assessing substrate turnover in humans in that they do not expose subjects to ionizing radiation and they provide positional isotopomer information, which in turn, can be used to assess flux thru critical metabolic pathways. The major disadvantage to the clinical investigator is that they require highly skilled expertise and expensive analytical equipment for their analysis. The Yale-DERC Clinical Metabolism Core overcomes these limitations by providing the personnel, methodology, and instrumentation for the centralized analysis of stable isotopic enrichment of biochemical compounds using state-of-the-art Gas Chromatographic-Mass Spectrometric (GC-MS), Liquid Chromatographic-Mass Spectrometric-Mass Spectrometric (LC-MS-MS) and nuclear magnetic resonance spectroscopy (NMR) spectroscopic methods. This core measures isotopic enrichments in metabolites (amino acids, glucose, glycogen, urea, and glucuronide conjugates) purified from plasma, urine or tissues by ion exchange chromatography, by: 13C, 1H or 31P NMR spectroscopy or combined GC-MS or LC-MS-MS analysis. The primary purpose of the Yale-DERC Clinical Metabolism core is to:

• to make GC-MS, LC-MS-MS and NMR analyses available to DERC participants,
• to save money and effort by reducing duplication of personnel required to program and operate the spectrometers,
• to provide standardized procedures to insure the accuracy of sample analysis and
• to assist DERC participants in the design and interpretation of experiments which require GC-MS, LC-MS-MS or NMR analysis.