Heavy Water Labeling : Extracting a Big Change from Small Variations

Abstract

Mass spectrometry (MS) has revolutionized biochemical analysis in terms of sensitivity, specificity, and speed. A fundamental drawback of MS as an analytical technique is the poor ability of quantification. To overcome this limitation, stable isotope labeling has been extensively employed for both relative and absolute quantification based on MS. In most quantitative MS experiments, complete labeling of target analytes with a specific type of heavy isotope (e.g., 2H, 13C, or 15N) is designed for simple distinction of isotope-labeled compounds from non-labeled counterparts in a mass spectrum. However, the use of isotope labeling is a cumbersome practice mainly due to high cost and long time to achieve complete labeling. An alternative method to introduce an isotope to biomolecules is indirect deuterium labeling via heavy water (2H2O) administration, which results in strikingly different patterns of mass spectra because of partial isotope enrichment. In this presentation, properties and characteristics of 2H2O labeling are discussed along with its limitations and challenges for applications in MS-based quantification studies.