CoChat
Sign Up
Cited by 209Liver Disease and TransplantationAmino Acid Enzymes and MetabolismMetabolism and Genetic Disorders

The DOI matches its Crossref record; 214 of the 215 references it cites were found in a registry or an index.

Astrocyte Glutamine Synthetase: Importance in Hyperammonemic Syndromes and Potential Target for Therapy

Open access
Brusilow, Saul W., Koehler, Raymond C., Traystman, Richard J., Cooper, Arthur J.L.·2010·Neurotherapeutics
DOI 10.1016/j.nurt.2010.05.015PMC PMC2975543
Open this paper in CoChat — free accountOpen PDF

Abstract

Many theories have been advanced to explain the encephalopathy associated with chronic liver disease and with the less common acute form. A major factor contributing to hepatic encephalopathy is hyperammonemia resulting from portacaval shunting and/or liver damage. However, an increasing number of causes of hyperammonemic encephalopathy have been discovered that present with the same clinical and laboratory features found in acute liver failure, but without liver failure. Here, we critically review the physiology, pathology, and biochemistry of ammonia (i.e., NH3 plus NH4+) and show how these elements interact to constitute a syndrome that clinicians refer to as hyperammonemic encephalopathy (i.e., acute liver failure, fulminant hepatic failure, chronic liver disease). Included will be a brief history of the status of ammonia and the centrality of the astrocyte in brain nitrogen metabolism. Ammonia is normally detoxified in the liver and extrahepatic tissues by conversion to urea and glutamine, respectively. In the brain, glutamine synthesis is largely confined to astrocytes, and it is generally accepted that in hyperammonemia excess glutamine compromises astrocyte morphology and function. Mechanisms postulated to account for this toxicity will be examined with emphasis on the osmotic effects of excess glutamine (the osmotic gliopathy theory). Because hyperammonemia causes osmotic stress and encephalopathy in patients with normal or abnormal liver function alike, the term "hyperammonemic encephalopathy" can be broadly applied to encephalopathy resulting from liver disease and from various other diseases that produce hyperammonemia. Finally, the possibility that a brain glutamine synthetase inhibitor may be of therapeutic benefit, especially in the acute form of liver disease, is discussed.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.nurt.2010.05.015

Cites

214 of 214 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Research works printed but not linked: 4

  1. van Caulaert, 1932, Ammoniémie expérimentale après ingestion de chlorure d'ammonium chez l'homme à l'état normal et pathologique, Compt Rend Soc Biol (Paris), 111, 50
  2. van Caulaert, 1932, Troubles provoqués par l'ingestion de sels ammoniacaux chez l'homme atteint de cirrhose de Laënnec, Compt Rend Soc Biol (Paris), 111, 739
  3. Norenberg, 1977, A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy, Lab Invest, 36, 618
  4. Sørensen, 2007, New findings on cerebral ammonia uptake in HE using functional 13N-ammonia PET, Metab Brain Dis, 22, 277, 10.1007/s11011-007-9066-1 · DOI

Cited by

Sorted by citations

See all 209

Related

See all

Metadata

Authors
Brusilow, S. W., Koehler, R. C., Traystman, R. J., & Cooper, A. J. L.
Affiliations
  • Johns Hopkins University (US)
  • University of Colorado Denver (US)
  • New York Medical College (US)
Corresponding author
  • Brusilow, Saul W.
  • Cooper, Arthur J.L.
ORCID
Venue
Neurotherapeutics
Publisher
Elsevier BV
Published
2010-10
Volume
7
Issue
4
Pages
452-470
ISSN
1878-7479 (ISSN-L)
DOI
10.1016/j.nurt.2010.05.015
PMC
PMC2975543
OpenAlex
W2104703549
Cited by
209
References
215
Citations by year
2026: 9 · 2025: 13 · 2024: 10 · 2023: 10 · 2022: 16 · 2021: 17 · 2020: 7 · 2019: 11 · 2018: 14 · 2017: 11 · 2016: 14 · 2015: 13 · 2014: 23 · 2013: 16 · 2012: 16
FWCI
1.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurotherapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns025275-14)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 16739, R01DK016739)
  • National Institute of Neurological Disorders and Stroke (R01NS046072, NS 25275)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
hyperammonemic encephalopathy, glutamine synthetase, astrocytes, hyperammonemia, chronic liver disease, acute liver failure, ammonia detoxification, glutamine synthetase inhibitors, portacaval shunt
MeSH terms
Animals, Astrocytes, Enzyme Inhibitors, Glutamate-Ammonia Ligase, Hepatic Encephalopathy, Humans, Hyperammonemia

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review