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The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling

Abstract

The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.
Authors:
Publication Date:
Nov 01, 1995
Product Type:
Thesis/Dissertation
Report Number:
FFI-95-05140
Reference Number:
SCA: 553006; PA: AIX-28:063869; EDB-97:139311; SN: 97001854828
Resource Relation:
Other Information: DN: Reprints of six previously printed papers are attached.; TH: Thesis (Dr. Scient.).; PBD: Nov 1995
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; AMINO ACIDS; BIOCHEMICAL REACTION KINETICS; BRAIN; METABOLISM; CARBON 13; CARBON 14; CEREBRAL CORTEX; LABELLED COMPOUNDS; NERVE CELLS; NMR SPECTRA
OSTI ID:
536887
Research Organizations:
Forsvarets Forskningsinstitutt, Kjeller (Norway)
Country of Origin:
Norway
Language:
English
Other Identifying Numbers:
Other: ON: DE98600406; ISBN 82-464-0032-0; TRN: NO9700104063869
Availability:
INIS; OSTI as DE98600406
Submitting Site:
NWN
Size:
106 p.
Announcement Date:
Nov 06, 1997

Citation Formats

Hassel, B. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling. Norway: N. p., 1995. Web.
Hassel, B. The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling. Norway.
Hassel, B. 1995. "The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling." Norway.
@misc{etde_536887,
title = {The cerebral metabolism of amino acids and related metabolites as studied by {sup 13}C and {sup 14}C labelling}
author = {Hassel, B}
abstractNote = {The present investigations show the feasibility of analyzing the cerebral metabolism of amino acids and related metabolites by {sup 13}C-and {sup 14}C-labelling using labelled acetate and glucose as markers for glial and neuronal metabolism, respectively. Using [{sup 13}C]acetate, it was shown that glial cells export {approx}60% of their TCA cycle intermediates, mostly as glutamine, and that this glutamine is used by neurons partly as an energy reserve, and partly it is converted directly to glutamate and GABA. Using [{sup 13}C]glucose, the glial process or pyruvate carboxylation was shown to compensate fully for the loss of glutamine. The mechanism of action of two neurotoxins, fluorocitrate and 3-nitropropionate was elucidated. The latter toxin was shown to inhibit the TCA cycle of GABAergic neurons selectively. Formation of pyruvate and lactate from glial TCA cycle intermediates was demonstrated in vivo. This pathway may be important for glial inactivation of transmitter glutamate and GABA. The results illustrate glianeuronal interactions, and they suggest the applicability of {sup 13}CNMR spectroscopy to the detailed study of the cerebral metabolism of amino acids in the intact, unanesthetized human brain. 174 refs.}
place = {Norway}
year = {1995}
month = {Nov}
}