A mathematical model of compartmentalized neurotransmitter metabolism in the human brain.

Details

Serval ID
serval:BIB_76D29075162B
Type
Article: article from journal or magazin.
Collection
Publications
Title
A mathematical model of compartmentalized neurotransmitter metabolism in the human brain.
Journal
American Journal of Physiology. Endocrinology and Metabolism
Author(s)
Gruetter R., Seaquist E.R., Ugurbil K.
ISSN
0193-1849 (Print)
ISSN-L
0193-1849
Publication state
Published
Issued date
2001
Volume
281
Number
1
Pages
E100-E112
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
After administration of enriched [1-13C]glucose, the rate of 13C label incorporation into glutamate C4, C3, and C2, glutamine C4, C3, and C2, and aspartate C2 and C3 was simultaneously measured in six normal subjects by 13C NMR at 4 Tesla in 45-ml volumes encompassing the visual cortex. The resulting eight time courses were simultaneously fitted to a mathematical model. The rate of (neuronal) tricarboxylic acid cycle flux (V(PDH)), 0.57 +/- 0.06 micromol. g(-1). min(-1), was comparable to the exchange rate between (mitochondrial) 2-oxoglutarate and (cytosolic) glutamate (Vx), 0.57 +/- 0.19 micromol. g(-1). min(-1)), which may reflect to a large extent malate-aspartate shuttle activity. At rest, oxidative glucose consumption [CMR(Glc(ox))] was 0.41 +/- 0.03 miccromol. g(-1). min(-1), and (glial) pyruvate carboxylation (VPC) was 0.09 +/- 0.02 micromol. g(-1). min(-1). The flux through glutamine synthetase (Vsyn) was 0.26 +/- 0.06 micromol. g(-1). min(-1). A fraction of Vsyn was attributed to be from (neuronal) glutamate, and the corresponding rate of apparent glutamatergic neurotransmission (VNT) was 0.17 +/- 0.05 micromol. g(-1). min(-1). The ratio [VNT/CMR(Glcox)] was 0.41 +/- 0.14 and thus clearly different from a 1:1 stoichiometry, consistent with a significant fraction (approximately 90%) of ATP generated in astrocytes being oxidative. The study underlines the importance of assumptions made in modeling 13C labeling data in brain.
Keywords
Algorithms, Brain/cytology, Brain Chemistry/physiology, Cytosol/metabolism, Energy Metabolism/physiology, Gas Chromatography-Mass Spectrometry, Gluconeogenesis/physiology, Glutamate Synthase/metabolism, Glutamic Acid/metabolism, Glutamine/metabolism, Humans, Kinetics, Magnetic Resonance Spectroscopy, Models, Biological, Models, Theoretical, Neurotransmitter Agents/metabolism
Pubmed
Web of science
Create date
04/08/2010 15:28
Last modification date
20/08/2019 14:33
Usage data