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Cerebral glutamine metabolism under hyperammonemia determined in vivo by localized (1)H and (15)N NMR spectroscopy.
MedLine Citation:
PMID:  22167234     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.Journal of Cerebral Blood Flow & Metabolism advance online publication, 14 December 2011; doi:10.1038/jcbfm.2011.173.
Authors:
Cristina Cudalbu; Bernard Lanz; João Mn Duarte; Florence D Morgenthaler; Yves Pilloud; Vladimir Mlynárik; Rolf Gruetter
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-14
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  -     ISSN:  1559-7016     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory for Functional and Metabolic Imaging (LIFMET), Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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