Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.1 (pyruvate carboxylase)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The principle substrate for brain metabolism is glucose, which provides both energy and the carbon skeletons of glutamate and glutamine, via the TCA cycle. The existence of two distinct cerebral metabolic compartments, neurons and glia, involved in glutamate and glutamine synthesis, respectively, is a widely accepted concept. In previous work, the relative glucose flux via pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) in adult rabbit brain, using 13C NMR isotopomer analysis of glutamate and glutamine, was quantified. In this work, manifestation of cerebral compartmentation in the near-term fetal rabbit was investigated, using the above approach. Following infusion of [U-13C]glucose into maternal circulation (1 mg/kg per min) for 60-70 min, fetal brains were excised and brain extracts were studied by 13C NMR. The labelling patterns of fetal cerebral metabolites differed from those observed in the young adult brain. The most significant differences were found for glutamine labelling patterns. We suggested that these differences are a result of increased utilization of non-labeled fuels, mainly beta-hydroxybutyrate (beta-HBA) in the glia, the site of glutamine synthesis. In addition, we have shown that acute exposure to elevated beta-HBA levels leads to increased uptake, but not utilization, into the fetal rabbit brain; no increase in uptake is observed in the adult brain. We have also demonstrated that during short-term starvation, although no changes are detected in plasma and cerebral glucose levels in the fetal and young adult brain, amino acid levels and energy metabolism are altered in the young adult brain.
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PMID:Energy fuel utilization by fetal versus young rabbit brain: a 13C MRS isotopomer analysis of [U-(13)C]glucose metabolites. 1127 79

The neurological consequences of diabetes mellitus have recently been receiving greater attention in both clinical and experimental settings. The deleterious effect of hyperglycemia and altered oxidative substrate availability on the diabetic brain is the subject of many studies. The aim of the present study was to examine the effect of the altered metabolic environment, namely, hyperglycemia and hyperketonemia, on glucose metabolism in the diabetic brain. More specifically, we examined the effect of diabetes on the glucose flux via the pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) pathways and subsequent metabolism in the tricarboxylic acid cycles in neurons and glia. To this end, [U-(13)C]glucose was infused into the circulation of alloxan-induced diabetic young adult rabbits, and the [(13)C]glucose metabolites were subsequently studied in brain extracts by (13)C-NMR. Significantly elevated brain glucose levels were found. In the hyperketonemic rabbits, elevated cerebral levels of beta-hydroxybutyrate (beta-HBA) were found. Alterations in the labeling patterns of glutamine in the hyperketonemic group lead to the conclusion that the elevated beta-HBA levels inhibit glucose metabolism, mostly in glia. This results in accumulation of glucose in the diabetic brain. In addition, altered levels of glutamine, glutamate, and GABA were also attributed to the effect of beta-HBA on brain metabolism. The possible role of these metabolic perturbations in causing neurological damage remains to be investigated.
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PMID:Effect of endogenous beta-hydroxybutyrate on glucose metabolism in the diabetic rabbit brain: a (13)C-magnetic resonance spectroscopy study of [U-(13)C]glucose metabolites. 1128 49

The aim of our research was to uncover perturbations in in-utero fetal cerebral metabolism resulting from hyperglycemia and hyperketonemia, which occur during maternal diabetes. Therefore, we examined the effects of glucose overload and hyperketonemia on glucose metabolism in the diabetic fetal brain; more specifically, the effect of diabetes on the glucose flux via pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) and subsequent metabolism in the fetal cerebral tricarboxylic acid (TCA) cycle were examined, as well as the effect of diabetes on energy fuel utilization in the neurons and glia. Diabetes was induced in pregnant rabbits, and towards term, [U-(13)C(6)]glucose was infused into maternal circulation, and [(13)C]glucose metabolites were subsequently studied in fetal brain extracts by (13)C MRS isotopomer analysis. Significantly elevated maternal and fetal plasma glucose levels (three- and up to fivefold, respectively) and fetal brain glucose levels (up to eightfold) accompanied by an increase of beta-hydroxybutyrate (beta-HBA) levels (approximately 20-fold) were found in the hyperketonemic diabetic animals, whereas fetal cerebral lactate levels were decreased. Alterations in the (13)C labeling patterns, mainly of glutamine, led us to suggest that the entry of beta-HBA-derived acetyl-CoA inhibits formation and entry of labeled glucose-derived acetyl-CoA into the TCA cycle, mainly in glia. Accumulation of glucose and the decrease in lactate levels in the fetal brain are most likely the result of an inhibitory effect of beta-HBA on glycolysis. In addition, loss of (13)C enrichment of TCA cycle intermediates and products, glutamate and glutamine, in the hyperketonemic diabetic fetal brain may be attributed to the effect of beta-HBA fuel utilization by the fetal brain.
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PMID:Effect of endogenous beta-hydroxybutyrate on brain glucose metabolism in fetuses of diabetic rabbits, studied by (13)C magnetic resonance spectroscopy. 1197 97