Metabolomics exact mass

This analysis revealed a set of ions that were strongly elevated in the IDH mutant-containing cell lines. The exact mass identified these ions as (R)-2-hydroxyglutarate (2HG), the sodium adduct of 2-HG, and the dehydrated product of 2-HG. In vitro experiments with recombinant IDH confirmed that the mutant enzyme, but not the wild-type enzyme, is able to produce 2-HG (Fig. 9). Finally, this correlation was demonstrated to be of clinical relevance because patients with mutated IDH had higher levels of 2-HG. This example highlights the utility of metabolomics in the characterization of enzyme-substrate interactions, in this case a mutated enzyme associated with cancer. Moreover, this work has opened up a new field dedicated towards understanding if and how this IDH mutation leads to cancer [31, 56, 57]. 

In comparison with NMR, mass spectrometry is more sensitive and, thus, can be used for compounds of lower concentration. While it is easily possible to measure picomoles of compounds, detection limits at the attomole levels can be reached. Mass spectrometry also has the ability to identify compounds through elucidation of their chemical structure by MS/MS and determination of their exact masses. This is true at least for compounds below 500 Da, the limit at which very high-resolution mass spectrometry can unambiguously determine the elemental composition. In 2005, this could only be done by FTICR. Orbitrap appears to be a good alternative, with a more limited mass range but a better signal-to-noise ratio. Furthermore, mass spectrometry allows relative concentration determinations to be made between samples with a dynamic range of about 10000. Absolute quantification is also possible but needs reference compounds to be used. It should be mentioned that if mass spectrometry is an important technique for metabolome analysis, another key tool is specific software to manipulate, summarize and analyse the complex multivariant data obtained. 

The accurate mass capabilities of Time-of-Flight (TOF) are useful in determining the composition of new carotenoids or carotenoid metabolites which have not previously been identified (Mercadante et ah, 1997 Lakshminarayana et ah, 2008 Kopec et ah, 2010). In addition, a TOF chamber (interfaced with MALDI or an ESI ion source) is often used with a targeted metabolomics approach, where determining the exact mass of a mixture of components is important to successfully differentiate carotenoids from a high level of background ions (Fraser et ah, 2007 Chu et ah, 2011). 

In Section 8.7, Table 8.18 shows exact masses and the isotope distribution for abundant isotopes of eleven chemical elements X that are of importance for organic chemistry, = H, C, N, 0, F, Si, P, S, Cl, Br, I. The following algorithms can also be used with any other set of chemical elements. For the following sections, we introduced another set of elements chosen particularly for the search of biomarkers in metabolomics... 

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