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.