MATHEMATICAL-MODELING OF THE CRITIC ACID CYCLE FOR THE ANALYSIS OF GLUTAMINE ISOTOPOMERS FROM CEREBELLAR ASTROCYTES INCUBATED WITH [1-C-13]GLUCOSE

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.