B. Kunnecke et al., CEREBRAL METABOLISM OF [1,2-C-13(2)]GLUCOSE AND [U-C-13(4)]3-HYDROXYBUTYRATE IN RAT-BRAIN AS DETECTED BY C-13 NMR-SPECTROSCOPY, NMR in biomedicine, 6(4), 1993, pp. 264-277
Citations number
58
Categorie Soggetti
Spectroscopy,"Radiology,Nuclear Medicine & Medical Imaging",Biophysics,"Medical Laboratory Technology
The metabolism of [1,2-C-13(2)]glucose and [(UC4)-C-13]3-hydroxybutyra
te was studied in rat brain with in vivo and in vitro C-13 NMR spectro
scopy, taking advantage, in particular, of homonuclear C-13-C-13 spin
coupling patterns. After infusion of [1,2-C-13(2)]glucose or [U-C-13(4
)]3-hydroxybutyrate into rats, the uptake of the substrates in brain a
nd their metabolism to [1-C-13]bicarbonate could be detected with in v
ivo C-13 NMR spectroscopy. At the end of the infusion experiment, meth
anol/HCl/HClO4 extracts of the brain tissue were further analysed by h
igh resolution C-13 NMR spectroscopy. The C-13 spin coupling patterns
revealed entirely different isotopomer distributions for the closely r
elated cerebral metabolites glutamate, glutamine and 4-aminobutyric ac
id. A quantitative analysis of the C-13 Spectra demonstrated (i) the e
xistence of two kinetically distinct pools of glutamate, (ii) a pronou
nced CO2 fixation via pyruvate carboxylase in the glial cells accounti
ng for as much as 38% of the oxaloacetate synthesis in the glial trica
rboxylic acid cycle, (iii) a cerebral pyruvate recycling system contri
buting maximally 17% of the pyruvate metabolism through the pyruvate d
ehydrogenase in neurons, and (iv) a predominant production of 4-aminob
utyric acid from glutamate synthesized in the neurons. In addition, th
e labelling pattern of N-acetyl aspartate upon infusion of labelled gl
ucose or 3-hydroxybutyrate provided insight into the synthesis of this
compound in mammalian brain. While the acetyl moiety originates from
the metabolic equivalent of the C-1-C-2 part of cerebral glutamate, th
e aspartyl moiety is not in direct contact with the intermediates of g
lycolysis or of the tricarboxylic acid cycles.