scholarly journals Hepatic glutamine synthetase augmentation enhances ammonia detoxification

2019 ◽  
Vol 42 (6) ◽  
pp. 1128-1135 ◽  
Author(s):  
Leandro R. Soria ◽  
Matthew Nitzahn ◽  
Angela De Angelis ◽  
Suhail Khoja ◽  
Sergio Attanasio ◽  
...  
2008 ◽  
Vol 86 (6) ◽  
pp. 469-476 ◽  
Author(s):  
Elena A. Kosenko ◽  
Natalia I. Venediktova ◽  
Andrey A. Kudryavtsev ◽  
Fazoil I. Ataullakhanov ◽  
Yury G. Kaminsky ◽  
...  

There are a number of pathological situations in which ammonia levels increase leading to hyperammonemia, which may cause neurological alterations and can lead to coma and death. Currently, there are no efficient treatments allowing rapid and sustained decrease of ammonia levels in these situations. A way to increase ammonia detoxification would be to increase its incorporation in glutamine by glutamine synthetase. The aim of this work was to develop a procedure to encapsulate glutamine synthetase in mouse erythrocytes and to assess whether administration of these erythrocytes containing glutamine synthetase (GS) reduce ammonia levels in hyperammonemic mice. The procedure developed allowed the encapsulation of 3 ± 0.25 IU of GS / mL of erythrocytes with a 70% cell recovery. Most metabolites, including ATP, remained unaltered in glutamine synthetase-loaded erythrocytes (named ammocytes by us) compared with native erythrocytes. The glutamine synthetase-loaded ammocytes injected in mice survived and retained essentially all of their glutamine synthetase activity for at least 48 h in vivo. Injection of these ammocytes into hyperammonemic mice reduced ammonia levels in the blood by about 50%. The results reported indicate that ammocytes are able to keep their integrity, normal energy metabolism, the inserted glutamine synthetase activity, and can be useful to reduce ammonia levels in hyperammonemic situations.


2010 ◽  
Vol 285 (13) ◽  
pp. 9516-9524 ◽  
Author(s):  
Youji He ◽  
Theodorus B. M. Hakvoort ◽  
S. Eleonore Köhler ◽  
Jacqueline L. M. Vermeulen ◽  
D. Rudi de Waart ◽  
...  

1990 ◽  
Vol 270 (2) ◽  
pp. 473-481 ◽  
Author(s):  
N A Farrow ◽  
K Kanamori ◽  
B D Ross ◽  
F Parivar

1. Rats were infused with 15NH4+ or L-[15N]alanine to induce hyperammonaemia, a potential cause of hepatic encephalopathy. HClO4 extracts of freeze-clamped brain, liver and kidney were analysed by 15N-n.m.r. spectroscopy in combination with biochemical assays to investigate the effects of hyperammonaemia on tissue concentrations of ammonia, glutamine, glutamate and urea. 2. 15NH4+ infusion resulted in a 36-fold increase in the concentration of blood ammonia. Cerebral glutamine concentration increased, with 15NH4+ incorporated predominantly into the gamma-nitrogen atom of glutamine. Incorporation into glutamate was very low. Cerebral ammonia concentration increased 5-10-fold. The results suggest that the capacity of glutamine synthetase for ammonia detoxification was saturated. 3. Pretreatment with the glutamine synthetase inhibitor L-methionine DL-sulphoximine resulted in 84% inhibition of [gamma-15N]glutamine synthesis, but incorporation of 15N into other metabolites was not observed. The result suggests that no major alternative pathway for ammonia detoxification, other than glutamine synthetase, exists in rat brain. 4. In the liver 15NH4+ was incorporated into urea, glutamine, glutamate and alanine. The specific activity of 15N was higher in the gamma-nitrogen atom of glutamine than in urea. A similar pattern was observed when [15N]alanine was infused. The results are discussed in terms of the near-equilibrium states of the reactions involved in glutamate and alanine formation, heterogeneous distribution in the liver lobules of the enzymes involved in ammonia removal and their different affinities for ammonia. 5. Synthesis of glutamine, glutamate and hippurate de novo was observed in kidney. Hippurate, as well as 15NH4+, was contributed by co-extracted urine. 6. The potential utility and limitations of 15N n.m.r. for studies of mammalian metabolism in vivo are discussed.


Hepatology ◽  
2016 ◽  
Vol 65 (1) ◽  
pp. 281-293 ◽  
Author(s):  
Theodorus B.M. Hakvoort ◽  
Youji He ◽  
Wim Kulik ◽  
Jacqueline L.M. Vermeulen ◽  
Suzanne Duijst ◽  
...  

Author(s):  
W. Kunath ◽  
E. Zeitler ◽  
M. Kessel

The features of digital recording of a continuous series (movie) of singleelectron TV frames are reported. The technique is used to investigate structural changes in negatively stained glutamine synthetase molecules (GS) during electron irradiation and, as an ultimate goal, to look for the molecules' “undamaged” structure, say, after a 1 e/Å2 dose.The TV frame of fig. la shows an image of 5 glutamine synthetase molecules exposed to 1/150 e/Å2. Every single electron is recorded as a unit signal in a 256 ×256 field. The extremely low exposure of a single TV frame as dictated by the single-electron recording device including the electron microscope requires accumulation of 150 TV frames into one frame (fig. lb) thus achieving a reasonable compromise between the conflicting aspects of exposure time per frame of 3 sec. vs. object drift of less than 1 Å, and exposure per frame of 1 e/Å2 vs. rate of structural damage.


2017 ◽  
Vol 43 (9) ◽  
pp. 1410 ◽  
Author(s):  
Xiao-Chun WANG ◽  
Hao-Ran ZHANG ◽  
Yi-Hao WEI ◽  
Xi-Ting JIA ◽  
Ming-Xin GU ◽  
...  

2013 ◽  
Vol 12 (7) ◽  
pp. 900-913 ◽  
Author(s):  
Hans-Gert Bernstein ◽  
Anne Tausch ◽  
Rebecca Wagner ◽  
Johann Steiner ◽  
Patrick Seeleke ◽  
...  

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