Ammonia toxicity and cerebral oxidative metabolism.

Ammonia toxicity and cerebral oxidative metabolism. Am. J. Physiol. 200(3) : 420-424. 1961. -Effects of NH&l on oxidative metabolism of cat cerebral cortex slices and mitochondria incubated in vitro were studied. In slices, addition of IO mM NH&l to the incubation medium resulted in significant (16%) reduction of O2 uptake, doubling of lactic acid production and marked increase of glucose utilization compared to control slices. Mitochondria showed a 30-407~ decrease of O2 consumption in the presence of I 5 mM NH&l when pyruvate or a-ketoglutarate were substrates, but little if any difference from controls with succinate, glutamic acid or y-aminobutyric acid as substrates. Pyruvate utilization by ammonia-treated mitochondria was inhibited to the same degree as O2 consumption and was not increased by supplementing the incubation medium with excess succinate. Additions of &ipoic acid, thiamine pyrophosphate or DPN to such preparations failed to reverse the NH&l effect. Satisfactory P/O ratios were obtained for all mitochondrial preparations. It is concluded that a primary toxic effect of ammonia on the brain may be direct interference with oxidative decarboxylation of pyruvic and a-ketoglutaric acids.