The Glycerophospho Metabolome and Its Influence on Amino Acid Homeostasis Revealed by Brain Metabolomics of GDE1(−/−) Mice

Kopp, Florian; Komatsu, Toshimitsu; Nomura, Daniel K.; Trauger, Sunia A.; Thomas, Jason R.; Siuzdak, Gary; Simón, Gabriel; Cravatt, Benjamin F.

doi:10.1016/j.chembiol.2010.06.009

Cited by 34 publications

(30 citation statements)

References 53 publications

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“…For instance, as shown by the heat map (Figure 3), some phospholipids exhibited pronounced regional variability with increasing/decreasing levels depending on the caudally decreasing gradient in gray matter. However, a number of specific glycerophosphoserines displayed significant contrasting levels between frontal and caudal brain regions (Figure 2, Figure 3), where they may serve as a metabolic reservoir for free serine and regulate serine-dependent neurotransmission (Kopp, et al, 2010). Another intriguing finding related to lipid metabolite patterns was a significant high level of cholesterol sulfate in cerebellum when compared to other brain regions.…”

Section: Resultsmentioning

confidence: 99%

Brain Region Mapping Using Global Metabolomics

Ivanišević¹,

Epstein²,

Kurczy³

et al. 2014

Chemistry & Biology

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SUMMARY Historically, studies of brain metabolism have been based on targeted analyses of a limited number of metabolites. Here we present a novel untargeted mass spectrometry-based metabolomics approach that has successfully uncovered differences in broad array of metabolites across anatomical regions of the mouse brain. The NSG immunodeficient mouse model was chosen because of its ability to undergo humanization leading to numerous applications in oncology and infectious disease research. Metabolic phenotyping by hydrophilic interaction liquid chromatography and nanostructure imaging mass spectrometry revealed unique water-soluble and lipid metabolite patterns between brain regions. Neurochemical differences in metabolic phenotypes were mainly defined by various phospholipids and several intriguing metabolites including carnosine, cholesterol sulfate, lipoamino acids, uric and sialic acid whose physiological roles in brain metabolism are poorly understood. This study lays important groundwork by defining regional homeostasis for the normal mouse brain to give context to the reaction to pathological events.

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Section: Resultsmentioning

confidence: 99%

Brain Region Mapping Using Global Metabolomics

Ivanišević¹,

Epstein²,

Kurczy³

et al. 2014

Chemistry & Biology

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“…Metabolite measurements were conducted using modified versions of previous procedures (Kopp et al, 2010; Nomura et al, 2010b). Details are described in Supplementary Materials.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Profiling Reveals PAFAH1B3 as a Critical Driver of Breast Cancer Pathogenicity

Mulvihill

Benjamin

et al. 2014

Chemistry & Biology

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Many studies have identified metabolic pathways that underlie cellular transformation, but the metabolic drivers of cancer progression remain less well understood. The Hippo transducer pathway has been shown to confer malignant traits on breast cancer cells. In this study, we used metabolic mapping platforms to identify biochemical drivers of cellular transformation and malignant progression driven through RAS and the Hippo pathway in breast cancer, and identified platelet activating factor acetylhydrolase 1B3 (PAFAH1B3) as a key metabolic driver of breast cancer pathogenicity that is upregulated in primary human breast tumors and correlated with poor prognosis. Metabolomic profiling suggests that PAFAH1B3 inactivation attenuates cancer pathogenicity through enhancing tumor-suppressing signaling lipids. Our studies provide a map of altered metabolism that underlies breast cancer progression and put forth PAFAH1B3 as a critical metabolic node in breast cancer.

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“…Metabolite measurements were conducted using modified versions of previous procedures (18,28). Details are provided in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity

Benjamin

Cozzo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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186

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Aberrant lipid metabolism is an established hallmark of cancer cells. In particular, ether lipid levels have been shown to be elevated in tumors, but their specific function in cancer remains elusive. We show here that the metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the synthesis of ether lipids, is up-regulated across multiple types of aggressive human cancer cells and primary tumors. We demonstrate that ablation of AGPS in cancer cells results in reduced cell survival, cancer aggressiveness, and tumor growth through altering the balance of ether lipid, fatty acid, eicosanoid, and fatty acidderived glycerophospholipid metabolism, resulting in an overall reduction in the levels of several oncogenic signaling lipids. Taken together, our results reveal that AGPS, in addition to maintaining ether lipids, also controls cellular utilization of fatty acids, favoring the generation of signaling lipids necessary for promoting the aggressive features of cancer.cancer metabolism | metabolomics | lipid signaling lysophosphatidic acid | eicosanoids

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The Glycerophospho Metabolome and Its Influence on Amino Acid Homeostasis Revealed by Brain Metabolomics of GDE1(−/−) Mice

Cited by 34 publications

References 53 publications

Brain Region Mapping Using Global Metabolomics

Brain Region Mapping Using Global Metabolomics

Metabolic Profiling Reveals PAFAH1B3 as a Critical Driver of Breast Cancer Pathogenicity

Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity

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