Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of long-term application of corticosterone (CORT) s.c. the equivalent of cortisol in rats, on behavior, oxidative and energy metabolism in brain parietotemporal cortex and hippocampus of 1-year-old male Wistar rats. The data were compared with results derived from long-term and low dose intracerebroventricular application of the diabetogenic drug streptozotocin (STZ) known to inhibit the function of the neuronal insulin receptor and generating an insulin resistant brain state. CORT reduced both working and reference memory increasingly with time and running parallel to the STZ-induced deficit. The effect of CORT on the activities of the glycolytic enzymes hexokinase, phosphofructokinase, pyruvate kinase, glyceraldehyde-3-phosphodehydrogenase, lactate dehydrogenase and, in tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase equaled in both experimental conditions and in both regions studied: significant decreases of all enzyme activities except lactate dehydrogenase which increased between three and fourfold of normal. The CORT- and STZ-induced marked fall in ATP was in the same range in the regions studied. Differences became obvious in the concentration of creatine phosphate in parietotemporal cerebral cortex showing no decrease after CORT obviously due to a different susceptibility of the CORT-receptor. It is discussed that both CORT and STZ may act on the neuronal insulin receptor in a similar way. However, further studies are needed on the gene expression of insulin and the insulin receptor and its protein levels to clarify the exact action of CORT on the neuronal insulin receptor function.
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PMID:Long-term effects of corticosterone on behavior, oxidative and energy metabolism of parietotemporal cerebral cortex and hippocampus of rats: comparison to intracerebroventricular streptozotocin. 1867 62

Temporal lobe epilepsy is a common form of adult epilepsy and shows high resistance to treatment. Increasing evidence has suggested that metabolic dysfunction contributes to the development of seizures, with previous studies indicating impairments in brain glucose metabolism. Here we aim to elucidate which pathways involved in glucose metabolism are impaired, by tracing the hippocampal metabolism of injected [U-13C]glucose (i.p.) during the chronic stage of the pilocarpine-status epilepticus mouse model of epilepsy. The enrichment of 13C in the intermediates of glycolysis and the TCA cycle were quantified in hippocampal extracts using liquid chromatography-tandem mass spectroscopy, along with the measurement of the activities of enzymes in each pathway. We show that there is reduced incorporation of 13C in the intermediates of glycolysis, with the percentage enrichment of all downstream intermediates being highly correlated with those of glucose 6-phosphate. Furthermore, the activities of all enzymes in this pathway including hexokinase and phosphofructokinase were unaltered, suggesting that glucose uptake is reduced in this model without further impairments in glycolysis itself. The key findings were 33% and 55% losses in the activities of pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase, respectively, along with reduced 13C enrichment in TCA cycle intermediates. This lower 13C enrichment is best explained in part by the reduced enrichment in glycolytic intermediates, whereas the reduction of key TCA cycle enzyme activity indicates that TCA cycling is also impaired in the hippocampal formation. Together, these data suggest that multitarget approaches may be necessary to restore metabolism in the epileptic brain.
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PMID:Alterations in Cytosolic and Mitochondrial [U-13C]Glucose Metabolism in a Chronic Epilepsy Mouse Model. 3009 85


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