Toward ‘Omic Scale Metabolite Profiling: A Dual Separation–Mass Spectrometry Approach for Coverage of Lipid and Central Carbon Metabolism

Ivanisevic, Julijana; Zhu, Zheng-Jiang; Plate, Lars; Tautenhahn, Ralf; Chen, Stephen; O’Brien, Peter J.; Johnson, Caroline H.; Marletta, Michael A.; Patti, Gary J.; Siuzdak, Gary

doi:10.1021/ac401140h

Title: Toward ‘Omic Scale Metabolite Profiling: A Dual Separation–Mass Spectrometry Approach for Coverage of Lipid and Central Carbon Metabolism

Journal Article · Wed Jun 19 00:00:00 EDT 2013 · Analytical Chemistry

DOI:https://doi.org/10.1021/ac401140h· OSTI ID:1788443

Ivanisevic, Julijana ^[1]; Zhu, Zheng-Jiang ^[1]; Plate, Lars ^[1]; Tautenhahn, Ralf ^[1]; Chen, Stephen ^[1]; O’Brien, Peter J. ^[2]; Johnson, Caroline H. ^[1]; Marletta, Michael A. ^[1]; Patti, Gary J. ^[3]; Siuzdak, Gary ^[1]

The Scripps Research Inst., La Jolla, CA (United States)
La Jolla Laboratories, San Diego, CA (United States). Pfizer Worldwide Research and Development
Washington Univ., St. Louis, MO (United States)

Although the objective of any ‘omic science is broad measurement of its constituents, such coverage has been challenging in metabolomics because the metabolome is comprised of a chemically diverse set of small molecules with variable physical properties. While extensive studies have been performed to identify metabolite isolation and separation methods, these strategies introduce bias toward lipophilic or water-soluble metabolites depending on whether reversed-phase (RP) or hydrophilic interaction liquid chromatography (HILIC) is used, respectively. Here we extend our consideration of metabolome isolation and separation procedures to integrate RPLC/MS and HILIC/MS profiling. An aminopropyl-based HILIC/MS method was optimized on the basis of mobile-phase additives and pH, followed by evaluation of reproducibility. When applied to the untargeted study of perturbed bacterial metabolomes, the HILIC method enabled the accurate assessment of key, dysregulated metabolites in central carbon pathways (e.g., amino acids, organic acids, phosphorylated sugars, energy currency metabolites), which could not be retained by RPLC. To demonstrate the value of the integrative approach, bacterial cells, human plasma, and cancer cells were analyzed by combined RPLC/HILIC separation coupled to ESI positive/negative MS detection. In this work, the combined approach resulted in the observation of metabolites associated with lipid and central carbon metabolism from a single biological extract, using 80% organic solvent (ACN:MeOH:H2O 2:2:1). It enabled the detection of more than 30,000 features from each sample type, with the highest number of uniquely detected features by RPLC in ESI positive mode and by HILIC in ESI negative mode. Therefore, we conclude that when time and sample are limited, the maximum amount of biological information related to lipid and central carbon metabolism can be acquired by combining RPLC ESI positive and HILIC ESI negative mode analysis.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); California Institute of Regenerative Medicine; National Institutes of Health (NIH); National Institute on Aging (NIA)

Grant/Contract Number:: AC02-05CH11231; FG02-07ER64325

OSTI ID:: 1788443

Journal Information:: Analytical Chemistry, Vol. 85, Issue 14; ISSN 0003-2700

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Metabolomics guided pathway analysis reveals link between cancer metastasis, cholesterol sulfate, and phospholipids Johnson, Caroline H.; Santidrian, Antonio F.; LeBoeuf, Sarah E. Cancer & Metabolism, Vol. 5, Issue 1 https://doi.org/10.1186/s40170-017-0171-2	journal	October 2017
Untargeted mass spectrometry discloses plasma solute levels poorly controlled by hemodialysis Sirich, Tammy L.; Aronov, Pavel A.; Fullman, Jonathan PLOS ONE, Vol. 12, Issue 11 https://doi.org/10.1371/journal.pone.0188315	journal	November 2017
Cancer proteome and metabolite changes linked to SHMT2 Tong, Jiefei; Krieger, Jonathan R.; Taylor, Paul PLOS ONE, Vol. 15, Issue 9 https://doi.org/10.1371/journal.pone.0237981	journal	September 2020
Metabolic drift in the aging brain Ivanisevic, Julijana; Stauch, Kelly L.; Petrascheck, Michael Aging, Vol. 8, Issue 5 https://doi.org/10.18632/aging.100961	journal	May 2016
MetabNet: An R Package for Metabolic Association Analysis of High-Resolution Metabolomics Data Uppal, Karan; Soltow, Quinlyn A.; Promislow, Daniel E. L. Frontiers in Bioengineering and Biotechnology, Vol. 3 https://doi.org/10.3389/fbioe.2015.00087	journal	June 2015
Cigarette Smoke Reduces Fatty Acid Catabolism, Leading to Apoptosis in Lung Endothelial Cells: Implication for Pathogenesis of COPD Gong, Jiannan; Zhao, Hui; Liu, Tanzhen Frontiers in Pharmacology, Vol. 10 https://doi.org/10.3389/fphar.2019.00941	journal	August 2019
Application of the amniotic fluid metabolome to the study of fetal malformations, using Down syndrome as a specific model Huang, Jun; Mo, Jinhua; Zhao, Guili Molecular Medicine Reports, Vol. 16, Issue 5 https://doi.org/10.3892/mmr.2017.7507	journal	May 2017

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