Metabolic profiling using stable isotope tracer technology GC/MS

Every major development in medicine utilized some form of tracing methods, which bring disease specific changes to the surface from beneath the maze of gene or protein interactions. Genetics greatly benefited from gene specific amplification methods such as the polymerase chain reaction known as PCR and monoclonal antibodies continuously aid in the development of proteomics.

Metabolic profiling using stable isotope tracer technology and gas chromatography/mass spectrometry (GC/MS), measures the substrate redistribution within major metabolic pathways in living cells/organisms. This technique has demonstrated that detailed mechanisms of diseases that transformed human cells exhibit profound alterations in metabolic network characteristics. Forcing reversions of such metabolic shifts back toward more normal patterns of carbon flow and substrate utilization is novel and key method of treating diseases. By revealing the disease specific metabolic changes in substrate utilization and macromolecule synthesis occurring in diseased cells, metabolic profiling allows drug developers to identify the metabolic steps that control cellular phenotype. The information thus gained can both readily identify molecular targets for new drugs to be developed and greatly assist in the screening of new candidates to determine whether they have desired metabolic effects to treat disease. Applications so far have elucidated disease mechanisms such as thiamine responsive megaloblastic anemia, significant metabolic network abnormalities in cancer and new drug resistance mechanisms in the targeted genetic approach of anti-leukemia drug development efforts.

The use of chromatography and mass spectrometry play a key roll in our patent pending metabolic profiling methods. My discussion will focus on our use and the impact of mass spectrometry in our effort to measure stable isotope labeled substrate redistribution within major metabolic pathways in living cells and organisms.