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Cerebral glutamine metabolism under hyperammonemia determined in vivo by localized (1)H and (15)N NMR spectroscopy

Cudalbu, Cristina; Lanz, Bernard; Duarte, João M N LU ; Morgenthaler, Florence D; Pilloud, Yves; Mlynárik, Vladimir and Gruetter, Rolf (2012) In Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 32(4). p.696-708
Abstract

Brain glutamine synthetase (GS) is an integral part of the glutamate-glutamine cycle and occurs in the glial compartment. In vivo Magnetic Resonance Spectroscopy (MRS) allows noninvasive measurements of the concentrations and synthesis rates of metabolites. (15)N MRS is an alternative approach to (13)C MRS. Incorporation of labeled (15)N from ammonia in cerebral glutamine allows to measure several metabolic reactions related to nitrogen metabolism, including the glutamate-glutamine cycle. To measure (15)N incorporation into the position 5N of glutamine and position 2N of glutamate and glutamine, we developed a novel (15)N pulse sequence to simultaneously detect, for the first time, [5-(15)N]Gln and [2-(15)N]Gln+Glu in vivo in the rat... (More)

Brain glutamine synthetase (GS) is an integral part of the glutamate-glutamine cycle and occurs in the glial compartment. In vivo Magnetic Resonance Spectroscopy (MRS) allows noninvasive measurements of the concentrations and synthesis rates of metabolites. (15)N MRS is an alternative approach to (13)C MRS. Incorporation of labeled (15)N from ammonia in cerebral glutamine allows to measure several metabolic reactions related to nitrogen metabolism, including the glutamate-glutamine cycle. To measure (15)N incorporation into the position 5N of glutamine and position 2N of glutamate and glutamine, we developed a novel (15)N pulse sequence to simultaneously detect, for the first time, [5-(15)N]Gln and [2-(15)N]Gln+Glu in vivo in the rat brain. In addition, we also measured for the first time in the same experiment localized (1)H spectra for a direct measurement of the net glutamine accumulation. Mathematical modeling of (1)H and (15)N MRS data allowed to reduce the number of assumptions and provided reliable determination of GS (0.30±0.050 μmol/g per minute), apparent neurotransmission (0.26±0.030 μmol/g per minute), glutamate dehydrogenase (0.029±0.002 μmol/g per minute), and net glutamine accumulation (0.033±0.001 μmol/g per minute). These results showed an increase of GS and net glutamine accumulation under hyperammonemia, supporting the concept of their implication in cerebral ammonia detoxification.

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published
keywords
Ammonia, Animals, Brain, Glutamate-Ammonia Ligase, Glutamic Acid, Glutamine, Hyperammonemia, Magnetic Resonance Spectroscopy, Male, Models, Biological, Nitrogen Isotopes, Rats, Rats, Sprague-Dawley, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
volume
32
issue
4
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:84859432226
ISSN
1559-7016
DOI
10.1038/jcbfm.2011.173
language
English
LU publication?
no
id
6fa89237-e576-45f0-a124-79455aa38fb2
date added to LUP
2017-10-19 15:12:50
date last changed
2017-10-24 10:39:03
@article{6fa89237-e576-45f0-a124-79455aa38fb2,
  abstract     = {<p>Brain glutamine synthetase (GS) is an integral part of the glutamate-glutamine cycle and occurs in the glial compartment. In vivo Magnetic Resonance Spectroscopy (MRS) allows noninvasive measurements of the concentrations and synthesis rates of metabolites. (15)N MRS is an alternative approach to (13)C MRS. Incorporation of labeled (15)N from ammonia in cerebral glutamine allows to measure several metabolic reactions related to nitrogen metabolism, including the glutamate-glutamine cycle. To measure (15)N incorporation into the position 5N of glutamine and position 2N of glutamate and glutamine, we developed a novel (15)N pulse sequence to simultaneously detect, for the first time, [5-(15)N]Gln and [2-(15)N]Gln+Glu in vivo in the rat brain. In addition, we also measured for the first time in the same experiment localized (1)H spectra for a direct measurement of the net glutamine accumulation. Mathematical modeling of (1)H and (15)N MRS data allowed to reduce the number of assumptions and provided reliable determination of GS (0.30±0.050 μmol/g per minute), apparent neurotransmission (0.26±0.030 μmol/g per minute), glutamate dehydrogenase (0.029±0.002 μmol/g per minute), and net glutamine accumulation (0.033±0.001 μmol/g per minute). These results showed an increase of GS and net glutamine accumulation under hyperammonemia, supporting the concept of their implication in cerebral ammonia detoxification.</p>},
  author       = {Cudalbu, Cristina and Lanz, Bernard and Duarte, João M N and Morgenthaler, Florence D and Pilloud, Yves and Mlynárik, Vladimir and Gruetter, Rolf},
  issn         = {1559-7016},
  keyword      = {Ammonia,Animals,Brain,Glutamate-Ammonia Ligase,Glutamic Acid,Glutamine,Hyperammonemia,Magnetic Resonance Spectroscopy,Male,Models, Biological,Nitrogen Isotopes,Rats,Rats, Sprague-Dawley,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {4},
  pages        = {696--708},
  publisher    = {Nature Publishing Group},
  series       = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
  title        = {Cerebral glutamine metabolism under hyperammonemia determined in vivo by localized (1)H and (15)N NMR spectroscopy},
  url          = {http://dx.doi.org/10.1038/jcbfm.2011.173},
  volume       = {32},
  year         = {2012},
}