M. Merle et al., MATHEMATICAL-MODELING OF THE CRITIC ACID CYCLE FOR THE ANALYSIS OF GLUTAMINE ISOTOPOMERS FROM CEREBELLAR ASTROCYTES INCUBATED WITH [1-C-13]GLUCOSE, European journal of biochemistry, 239(3), 1996, pp. 742-751
A mathematical model of the citric acid cycle devoted to the analysis
of C-13-NMR data was developed for determining the relative flux of mo
lecules through the anaplerotic versus oxidative pathways and the rela
tive pyruvate carboxylase versus pyruvate dehydrogenase activities. Di
fferent variants of the model were considered depending on the reversi
bility of the conversion of fumarate into malate and oxaloacetate. The
model also included the possibility of orientation-conserved transfer
of the four-carbon citric acid cycle intermediates, leading to conver
sion of succinyl-CoA C1 into either malate C1 or C4. Lt was used to an
alyse NMR data from glutamine isotopomers produced by cerebellar astro
cytes incubated with [1-C-13]glucose. Partial cycling (39%) between ox
aloacetate and fumarate was evident from the analysis. Application of
the model to glutamate isotopomers from granule cells incubated with [
1-C-13]glucose [Martin, M., Portals, J. C., Labouesse, J., Canioni, P.
& Merle, M. (1993) Eur. J. Biochem. 217, 617-625] indicated that tota
l cycling of oxaloacetate into fumarate was, in this case, required to
get the best fit. The results emphasized some important differences i
n carbon metabolism between cerebellar astrocytes and granule cells co
ncerning the sources of carbon fuelling the citric acid cycle and the
carbon fluxes on different pathways.