Mass spectrometric studies on brain metabolism, using stable isotopes

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Abstract
In fields related to biomedicine, mass spectrometry has been applied to metabolism research and chemical structural analysis. The introduction of stable isotopes has advanced research related to in vivo metabolism. Stable‐isotope labeling combined with mass spectrometry appears to be a superior method for the metabolism studies, because it compensates for the shortcomings of conventional techniques that use radioisotopes. Biomolecules labeled with stable isotopes have provided solid evidence of their metabolic pathways. Labeled large molecules, however, cannot homogeneously mix in vivo with the corresponding endogenous pools. To overcome that problem, small tracers labeled with stable isotopes have been applied to in vivo studies because they can diffuse and attain a homogeneous distribution throughout the inter‐ and intracellular spaces. In particular, D2O‐labeling methods have been used for studies of the metabolism in different organs, including the brain, which is isolated from other extraneural organs by the blood–brain barrier (BBB). Cellular components, such as lipids, carbohydrates, proteins, and DNA, can be endogenously and concurrently labeled with deuterium, and their metabolic fluxes examined by mass spectrometry. Application of the D2O‐labeling method to the measurements of lipid metabolism and membrane turnover in the brain is described, and the potential advantages of this method are discussed in this review. This methodology also appears to have the potential to be applied to dynamic and functional metabolomics. © 2005 Wiley Periodicals, Inc., Mass Spec Rev 24:865–886, 2005