Dataset Information

Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [¹³C]-Glycerate Probes.

ABSTRACT: The interplay between glycolysis and gluconeogenesis is central to carbohydrate metabolism. Here, we describe novel methods to assess carbohydrate metabolism using [¹³C]-probes derived from glycerate, a molecule whose metabolic fate in mammals remains underexplored. Isotope-based studies were conducted via NMR and mass spectrometry analyses of freeze-clamped liver tissue extracts after [2,3-¹³C₂]glycerate infusion. The ex vivo investigations were correlated with in vivo measurements using hyperpolarized [1-¹³C]glycerate. Application of [¹³C]glycerate to N-nitrosodiethylamine (DEN)-treated rats provided further assessments of intermediary carbohydrate metabolism in hepatocellular carcinoma. This method afforded direct analyses of control versus DEN tissues, and altered ratios of ¹³C metabolic products as well as unique glycolysis intermediates were observed in the DEN liver/tumor. Isotopomer studies showed increased glycerate uptake and altered carbohydrate metabolism in the DEN rats.

SUBMITTER: Chen J

PROVIDER: S-EPMC9187054 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [13C]-Glycerate Probes.

Chen Jun J LaGue Evan E Li Junjie J Yang Chendong C Hackett Edward P EP Mendoza Manuel M Alger Jeffry R JR DeBerardinis Ralph J RJ Corbin Ian R IR Billingsley Kelvin L KL Park Jae Mo JM

Analysis & sensing 20210914 4

The interplay between glycolysis and gluconeogenesis is central to carbohydrate metabolism. Here, we describe novel methods to assess carbohydrate metabolism using [13C]-probes derived from glycerate, a molecule whose metabolic fate in mammals remains underexplored. Isotope-based studies were conducted via NMR and mass spectrometry analyses of freeze-clamped liver tissue extracts after [2,3-13C2]glycerate infusion. The ex vivo investigations were correlate ...[more]

PMID: 35693130

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Project description:Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than a year following diagnosis. Although bioinformatic analyses have indicated differentially expressed genes and cancer related mutations in HCC, integrated genetic and metabolic pathway analyses remain to be investigated. Herein, gene (i.e. messenger RNA, mRNA) enrichment analysis was performed to delineate significant alterations of metabolic pathways in HCC. The objective of this study was to investigate the pathway of aspartate metabolism in HCC of humans. Coupled with transcriptomic (i.e. mRNA) and NMR based metabolomics of human tissue extracts, we utilized liquid chromatography mass spectrometry based metabolomics analysis of stable [U-(13) C6 ]glucose metabolism or [U-(13) C5 ,(15) N2 ]glutamine metabolism of HCC cell culture. Our results indicated that aspartate metabolism is a significant and differentiable metabolic pathway of HCC compared with non-tumor liver (p value?<?0.0001). In addition, branched-chain amino acid metabolism (p value?<?0.0001) and tricarboxylic acid metabolism (p value?<?0.0001) are significant and differentiable. Statistical analysis of measurable NMR metabolites indicated that at least two of the group means were significantly different for the metabolites alanine (p value?=?0.0013), succinate (p value?=?0.0001), lactate (p value?=?0.0114), glycerophosphoethanolamine (p value?=?0.015), and inorganic phosphate (p value?=?0.0001). However, (13) C isotopic enrichment analysis of these metabolites revealed less than 50% isotopic enrichment with either stable [U-(13) C6 ]glucose metabolism or [U-(13) C5 ,(15) N2 ]glutamine. This may indicate the differential account of total metabolite pool versus de novo metabolites from a (13) C labeled substrate. The ultimate translation of these findings will be to determine putative enzyme activity via (13) C labeling, to investigate targeted therapeutics against these enzymes, and to optimize the in vivo performance of (13) C MRI techniques.

Dataset Information

Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [¹³C]-Glycerate Probes.

Publications

Profiling Carbohydrate Metabolism in Liver and Hepatocellular Carcinoma with [<sup>13</sup>C]-Glycerate Probes.

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