Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism

Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered... Fumarase catalyzes the interconversion of fumarate and l‐malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt‐induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC–MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l‐malic acid, l‐aspartic acid, glycine and l‐glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biomedical Chromatography Wiley

Combined metabolomic and correlation networks analyses reveal fumarase insufficiency altered amino acid metabolism

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Copyright © 2018 John Wiley & Sons, Ltd.
ISSN
0269-3879
eISSN
1099-0801
D.O.I.
10.1002/bmc.4133
Publisher site
See Article on Publisher Site

Abstract

Fumarase catalyzes the interconversion of fumarate and l‐malate in the tricarboxylic acid cycle. Fumarase insufficiencies were associated with increased levels of fumarate, decreased levels of malate and exacerbated salt‐induced hypertension. To gain insights into the metabolism profiles induced by fumarase insufficiency and identify key regulatory metabolites, we applied a GC–MS based metabolomics platform coupled with a network approach to analyze fumarase insufficient human umbilical vein endothelial cells (HUVEC) and negative controls. A total of 24 altered metabolites involved in seven metabolic pathways were identified as significantly altered, and enriched for the biological module of amino acids metabolism. In addition, Pearson correlation network analysis revealed that fumaric acid, l‐malic acid, l‐aspartic acid, glycine and l‐glutamic acid were hub metabolites according to Pagerank based on their three centrality indices. Alanine aminotransferase and glutamate dehydrogenase activities increased significantly in fumarase deficiency HUVEC. These results confirmed that fumarase insufficiency altered amino acid metabolism. The combination of metabolomics and network methods would provide another perspective on expounding the molecular mechanism at metabolomics level.

Journal

Biomedical ChromatographyWiley

Published: Jan 1, 2018

Keywords: ; ; ;

References

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