Evidence map›Paper›PMID 28245547›Full record

ReviewBiology2017

Glutamine-Glutamate Cycle Flux Is Similar in Cultured Astrocytes and Brain and Both Glutamate Production and Oxidation Are Mainly Catalyzed by Aspartate Aminotransferase.

Leif Hertz, Douglas L Rothman

Open access · goldAbstract readReview
In one paragraph

Review in Biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 80 citations in OpenAlex.

  1. Article
  2. Review
  3. Mitochondrial CaBiomolecules · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Oxygen and the Spark of Human Brain Evolution: Complex Interactions of Metabolism and Cortical Expansion across Development and Evolution.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Rates of pyruvate carboxylase, glutamate and GABA neurotransmitter cycling, and glucose oxidation in multiple brain regions of the awake rat using a combination of [2-Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Leif HertzLaboratory of Brain Metabolic Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, Liaoning 110000, China. lhertz538@gmail.com.
Douglas L RothmanMagnetic Resonance Research Center, Radiology and Biomedical Engineering, Yale University, New Haven, CT 06520, USA. douglas.rothman@yale.edu.
China Medical University · CNResonance Research (United States) · US

Funding

13C MRS Studies of Brain Mitochondrial Metabolism in Insulin ResistanceR01NS087568 · NINDS · YALE UNIVERSITY · PI PETERSEN, KITT F, ROTHMAN, DOUGLAS LYLE · 2014 to 2018
$2.1M
Validation of GABA MRS as a Biomarker of InhibitionR01MH109159 · NIMH · YALE UNIVERSITY · PI BEHAR, KEVIN L, ROTHMAN, DOUGLAS LYLE · 2016 to 2019
$1.7M
NIMH NIH HHS R01 MH109159NINDS NIH HHS R01 NS087568
6 · The paper itself

Abstract

The glutamine-glutamate cycle provides neurons with astrocyte-generated glutamate/γ-aminobutyric acid (GABA) and oxidizes glutamate in astrocytes, and it returns released transmitter glutamate/GABA to neurons after astrocytic uptake. This review deals primarily with the glutamate/GABA generation/oxidation, although it also shows similarity between metabolic rates in cultured astrocytes and intact brain. A key point is identification of the enzyme(s) converting astrocytic α-ketoglutarate to glutamate and vice versa. Most experiments in cultured astrocytes, including those by one of us, suggest that glutamate formation is catalyzed by aspartate aminotransferase (AAT) and its degradation by glutamate dehydrogenase (GDH). Strongly supported by results shown in Table 1 we now propose that both reactions are primarily catalyzed by AAT. This is possible because the formation occurs in the cytosol and the degradation in mitochondria and they are temporally separate. High glutamate/glutamine concentrations abolish the need for glutamate production from α-ketoglutarate and due to metabolic coupling between glutamate synthesis and oxidation these high concentrations render AAT-mediated glutamate oxidation impossible. This necessitates the use of GDH under these conditions, shown by insensitivity of the oxidation to the transamination inhibitor aminooxyacetic acid (AOAA). Experiments using lower glutamate/glutamine concentration show inhibition of glutamate oxidation by AOAA, consistent with the coupled transamination reactions described here.

Indexed as

aspartate aminotransferaseastrocyte culturebrain metabolismglutamate dehydrogenaseglutamate-glutamine cycleglutamate oxidationglutamine synthetasemalate-aspartate shuttlemetabolic compartmentationnitrogen balance

Identifiers

PMID28245547
PMCPMC5372010
OpenAlexW2591243891

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.