Cerebral metabolism in hypoxic hypoxia. I. Pattern of activation of glycolysis: a re-evaluation.
In order to evaluate the pattern of activation of glycolysis in cerebral cortex during hypoxic hypoxia, lightly anesthetized rats were subjected to a lowering of arterial Po2 to about 25 mm Hg and brains were frozen in situ for metabolite analyses either 1, 2, 5, 15 or 30 min following the induction of hypoxia. The lactate and pyruvate concentrations increased progressively during the 30 min period of hypoxia. At 1 and 2 min there were decreases in G-6-P and F-6-P, and increases in FDP, DHAP and 3-PG, indicating activation of phosphofructokinase. At 5 min this pattern of changes was less pronounced and at 15 min it was absent in spite of the fact that the lactate and pyruvate concentrations were further increased. At 30 min F-6-P and F-6-P had further increased but the levels of DHAP, FDP and 3-PG were normal. Evidently, phosphofructokinase activation can only be detected in the early stages of hypoxia, i.e. when the maximal increase in glycolytic flux occurs and before there has been a corresponding activation of other rate-limiting enzymatic steps. Signs of activation of phosphofructokinase were observed in the absence of changes in tissue concentrations of ATP or AMP, with minimal elevation of NH4plus, and in spite of increased (or unchanged) levels of citrate. However, since there were small but significant increases in ADP at 1 and 2 min, and pH-independent decreases in phosphocreatine, the results indicate that hypoxia is accompanied by an initial imbalance between production and utilization of ATP. The metabolic consequences of this imbalance (decrease in phosphocreatine, increases in ADP and P1) may be at least partly responsible for activation of phosphofructokinase.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D002951:Citrates / Q000378:metabolism; D004789:Enzyme Activation; D005636:Fructosephosphates / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007773:Lactates / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000097:blood*; D010725:Phosphocreatine / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D002951:Citrates; D005636:Fructosephosphates; D005958:Glucosephosphates; D007773:Lactates; D011773:Pyruvates; D010725:Phosphocreatine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000641:Ammonia; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; D010100:Oxygen