Pyruvate metabolism in the brain of young rats intoxicated with organic and inorganic lead.
The activities of lipoyl dehydrogenase, aspartate transaminase, and alanine transaminase, and levels of lactate were estimated in cerebral cortex, cerebellum, and brainstem of rats intoxicated acutely with tetraethyl lead and chronically with lead acetate. A significant inhibition of lipoyl dehydrogenase was observed in both groups of animals, whereas transaminase activities were increased in inorganic lead toxicity. Oxidative decarboxylation and anaplerosis of pyruvate was assessed in brain slices using [1-14C]pyruvate. Pyruvate dehydrogenase activity was decreased in both organic and inorganic lead toxicity, whereas labelling of aspartate and alanine was increased in inorganic lead toxicity. In studies in vitro, lead acetate showed a more significant effect than tetraethyl lead. The higher anaerobic metabolism in inorganic lead toxicity, as evidenced by increased anaerobic lactate production by brain slices, could either be an adaptive mechanism or be due to the delayed maturation of brain in the developing rat. Such a mechanism does not occur in acute organic lead toxicity, as the compound brings about massive and rapid degenerative changes in brain, resulting in convulsive seizures and death of the animals.
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D008058:Dihydrolipoamide Dehydrogenase / Q000037:antagonists & inhibitors; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D007854:Lead / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013756:Tetraethyl Lead / Q000633:toxicity*
D007773:Lactates; D009942:Organometallic Compounds; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D013756:Tetraethyl Lead; D007854:Lead; D019344:Lactic Acid; D019289:Pyruvic Acid; D008058:Dihydrolipoamide Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C008261:lead acetate