Dicarboxylic acid fluxes during gluconeogenesis. No channelling of mitochondrial oxalacetate.
A rather complete model of the gluconeogenic pathway was used, with the known separate pools of mitochondrial and cytosolic oxalacetate, malate and aspartate. The fumarase, malate dehydrogenase and glutamate oxalacetate transaminase reactions were assumed to be isotopically actively reversible, but none at isotopic equilibrium. Malate was assumed to exchange actively between the mitochondria and cytosol, while aspartate exchange was more limited, in agreement with the known electrogenic nature of aspartate export from the mitochondria. This model was fit to 14C data obtained in hepatocyte studies, and to the whole rat 14C data obtained by Heath and Rose (Biochem J. 227, 851-876, 1985). The latter data were easily fit to our model, when a single mitochondrial oxalacetate pool was assumed. However, invoking two mitochondrial oxalacetate pools, as proposed by Heath and Rose, with the oxalacetate formed via pyruvate carboxylase preferentially channelled to gluconeogenesis, could not be fit with the known differences in scrambling in glucose and glutamate produced from L[3-14C]lactate.
Rognstad
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Whittier Diabetes Program, Department of Medicine, University of California, San Diego, La Jolla 92093-0983, USA.
D000818:Animals; D003998:Dicarboxylic Acids / Q000378:metabolism; D005943:Gluconeogenesis / Q000502:physiology*; D066298:In Vitro Techniques; D008433:Mathematics; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D010071:Oxaloacetates / Q000378:metabolism; D051381:Rats
D003998:Dicarboxylic Acids; D010071:Oxaloacetates