Dataset Information

Measurement of 13 C turnover into glutamate and glutamine pools in brain tumor patients.

ABSTRACT: Malignant brain tumors are known to utilize acetate as an alternate carbon source in the citric acid cycle for their bioenergetics. 13 C NMR-based isotopomer analysis has been used to measure turnover of 13 C-acetate carbons into glutamate and glutamine pools in tumors. Plasma from the patients infused with [1,2-13 C]acetate further revealed the presence of 13 C isotopomers of glutamine, glucose, and lactate in the circulation that were generated due to metabolism of [1,2-13 C]acetate by peripheral organs. In the tumor cells, [4-13 C] and [3,4-13 C]glutamate and glutamine isotopomers were generated from blood-borne 13 C-labeled glucose and lactate which were formed due to [1,2-13 C[acetate metabolism of peripheral tissues. [4,5-13 C] and [3,4,5-13 C]glutamate and glutamine isotopomers were produced from [1,2-13 C]acetyl-CoA that was derived from direct oxidation of [1,2-13 C] acetate in the tumor. Major portion of C4 13 C fractional enrichment of glutamate (93.3 ± 0.02%) and glutamine (90.9 ± 0.03%) were derived from [1,2-13 C]acetate-derived acetyl-CoA.

SUBMITTER: Pichumani K

PROVIDER: S-EPMC5763554 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Measurement of 13 C turnover into glutamate and glutamine pools in brain tumor patients.

Pichumani Kumar K Mashimo Tomoyuki T Vemireddy Vamsidhara V Ijare Omkar B OB Mickey Bruce E BE Malloy Craig R CR Marin-Valencia Isaac I Baskin David S DS Bachoo Robert M RM Maher Elizabeth A EA

FEBS letters 20171027 21

Malignant brain tumors are known to utilize acetate as an alternate carbon source in the citric acid cycle for their bioenergetics. 13 C NMR-based isotopomer analysis has been used to measure turnover of 13 C-acetate carbons into glutamate and glutamine pools in tumors. Plasma from the patients infused with [1,2-13 C]acetate further revealed the presence of 13 C isotopomers of glutamine, glucose, and lactate in the circulation that were generated due t ...[more]

PMID: 28963851

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Project description:Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101 . Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253 .

Dataset Information

Measurement of 13 C turnover into glutamate and glutamine pools in brain tumor patients.

Publications

Measurement of <sup>13</sup> C turnover into glutamate and glutamine pools in brain tumor patients.

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