Ammonia toxicity and cerebral oxidative metabolism

¹ Section of Clinical Neurochemistry, National Institute of Neurological Diseases and Blindness, National Institutes of Health, Bethesda, Maryland

Effects of NH₄Cl on oxidative metabolism of cat cerebral cortex slices and mitochondria incubated in vitro were studied. In slices, addition of 10 mm NH₄Cl 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 30–40% decrease of O₂ consumption in the presence of 15 mm NH₄Cl when pyruvate or -ketoglutarate were substrates, but little if any difference from controls with succinate, glutamic acid or -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 -lipoic acid, thiamine pyrophosphate or DPN to such preparations failed to reverse the NH₄Cl 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 -ketoglutaric acids.

This article has been cited by other articles:

				K. E. Jain and A. P. Farrell Influence of seasonal temperature on the repeat swimming performance of rainbow trout Oncorhynchus mykiss J. Exp. Biol., October 15, 2003; 206(20): 3569 - 3579. [Abstract] [Full Text] [PDF]