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Hexose diphosphates and phosphofructokinase in rat brain during development
G J Dombrowski1, K R Swiatek, K L Chao
1Institute on Disability and Human Development, University of Illinois at Chicago 60680.
Insights
Fructose 2,6-diphosphate and glucose 1,6-diphosphate levels in rat brains change with age, but do not explain increased glucose use during suckling. Enzyme sensitivity to citrate also varied with age.
Area of Science:
- Biochemistry
- Neuroscience
- Developmental Biology
Background:
- Fructose 2,6-diphosphate (F2,6BP) and glucose 1,6-diphosphate (G1,6BP) are key regulators of glycolysis.
- Understanding their role in brain glucose metabolism during development is crucial.
Purpose of the Study:
- To investigate the developmental changes in F2,6BP and G1,6BP concentrations in rat brain cortex and cerebellum.
- To assess the influence of these metabolites and enzyme sensitivity on cerebral glucose utilization during suckling.
Main Methods:
- Quantification of F2,6BP and G1,6BP in rat brain cortex and cerebellum at different developmental stages (gestation, suckling).
- Assay of 6-phosphofructo-1-kinase (PFK-1) activity and its sensitivity to citrate and allosteric effectors (F2,6BP, G1,6BP) in young and adult rats.
Main Results:
- Cortex F2,6BP decreased significantly from neonatal to adult levels, while G1,6BP increased 4-fold during the same period.
- Cerebellar F2,6BP and G1,6BP concentrations remained stable throughout development.
- Neonatal PFK-1 was less sensitive to citrate inhibition than adult PFK-1, with F2,6BP being a more potent allosteric effector than G1,6BP at relieving inhibition.
Conclusions:
- Developmental changes in F2,6BP and G1,6BP concentrations in the rat cortex do not account for the increased cerebral glucose utilization observed during suckling.
- Differential age-related sensitivity of PFK-1 to citrate and allosteric regulation by F2,6BP and G1,6BP does not explain the observed changes in glucose metabolism.
Abstract:
Fructose 2,6-diphosphate and glucose 1,6-diphosphate concentrations were determined during late gestation and over the course of suckling in rat brain cortex and cerebellum. Cortex fructose 2,6-diphosphate concentration was greatest in neonatal animals and gradually declined thereafter by 25% to reach the adult level at 15 days of age. In contrast, the glucose 1,6-diphosphate concentration increased 4-fold over the same period to reach its highest level by postnatal day 15. Neither cerebellar fructose 2,6-diphosphate nor glucose 1,6-diphosphate concentrations varied significantly. Six day cortex 6-phosphofructo-1-kinase was less sensitive to inhibition by citrate than the enzyme obtained from 15 day pups, and fructose 2,6-diphosphate was better than glucose 1,6-diphosphate at relieving the inhibition imposed by citrate at either age. It is suggested that the rise in cerebral glucose use which occurs during suckling cannot be attributed to either changes in the concentrations of fructose 2,6-diphosphate or glucose 1,6-diphosphate, or the age-related differential sensitivity of 6-phosphofructo-1-kinase toward these effectors.