Open AccessPartial Isotope Profiles Are Sufficient for Protein Turnover Analysis Using Closed-Form Equations of Mass Isotopomer Dynamics
Author(s) -
Rovshan G. Sadygov
Publication year - 2020
Publication title -
analytical chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.117
H-Index - 332
eISSN - 1520-6882
pISSN - 0003-2700
DOI - 10.1021/acs.analchem.0c03343
Subject(s) - isotopomers , chemistry , proteome , mass spectrometry , metabolome , isotope , biological system , stable isotope ratio , protein dynamics , protein turnover , proteomics , chromatography , metabolomics , computational chemistry , biochemistry , molecular dynamics , protein biosynthesis , organic chemistry , physics , quantum mechanics , molecule , gene , biology
Metabolic labeling with atom-based heavy isotopes, followed by liquid chromatography coupled with mass spectrometry (LC-MS), has been a powerful technique for studies of proteome and metabolome. In proteomics, the protein turnover of thousands of proteins can be estimated from the gradual incorporation of 2 H or 15 N in the diet. Software tools have been developed to automate the estimation of protein turnover. Traditionally, the turnover has been estimated using the time course of the depletion of the normalized abundance of monoisotopes. While the bioinformatic aspects of peak detection and integration, time course modeling, and uncertainty estimation have progressed, mass isotopomer dynamics during label incorporation has only been modeled from approximate approaches or numerical simulations. We derive closed-form equations that describe the dynamics of mass isotopomers during metabolic labeling with an atom-based stable isotope. The derived equations create an alternative method for estimating label incorporation. They also provide opportunities for estimation of precursor-product relationships in species or systems where they are unknown. The equations are useful in bioinformatic tools for analyzing mass spectral data from metabolic labeling.