Hexose monophosphate pathway activity in normal and hypoxic rat brain.
Experiments were undertaken to define the role of the alternative route of glucose metabolism in the hexose monophosphate pathway (HMP) during energy balanced, mild brain hypoxia. In similar hypoxic model in spite of the lack of the deficit of high energy compounds, the significant acceleration of glycolysis and inhibition of macromolecular syntheses (lipid, proteins, and nucleic acids) were previously observed. The HMP activity, although directly coupled to intracellular synthetic processes, has not been defined and little is known about the mechanisms of its regulation under brain hypoxia. HMP activity was examined in the rat brain in vivo by estimation of the increment of 6-phosphogluconate concentration after inhibition of its oxidation as achieved by injection of 6-aminonicotinamide. The activity of this alternative route of glucose metabolism was estimated to be 0.4 mmol/h/kg w.w. in the brain cortex and 0.7 mmol/h/kg w.w. in the brain stem. During 2 h of mild hypoxia (7% O2 in N2) the HMP activity dropped to 30% of control level, whereas during first hour of reoxygenation increased to 200% of control. Increased activity of HMP in posthypoxic brain during reoxygenation also was observed in vitro by measuring the rate of [1-14C]- and [6-14C]glucose conversion to 14CO2 in cerebral cortical slices. The possible mechanism of the rapid changes in the activity of HMP induced by hypoxia is discussed. The results suggest that the brain glucose metabolism under mild hypoxia is reoriented toward energy producing pathway (glycolysis) partially at the expense of HMP. The mechanism of this regulation seems not to be directly triggered by energy deficit. Activity of HMP in the brain is in accord with the intracellular synthetic processes and their demands on the metabolites produced by this pathway. Relying upon that, the posthypoxic stimulation of HMP would indicate the metabolic recovery during reoxygenation.
Domańska-Janik
K
K
Department of Neurochemistry, Polish Academy of Sciences, Warsaw.
D015120:6-Aminonicotinamide / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005942:Gluconates / Q000378:metabolism; D006019:Glycolysis; D006600:Hexosephosphates / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D005942:Gluconates; D006600:Hexosephosphates; D015120:6-Aminonicotinamide; C008884:6-phosphogluconic acid