Different responses of rat cerebral mitochondrial 2-oxoglutarate dehydrogenase activity to ammonia and hepatic encephalopathy in synaptic and nonsynaptic mitochondria

Abstract

Abstract The effects of in vitro treatment with ammonium chloride and acute hepatic encephalopathy (HE) induced by thioacetamide treatment (TAA), on the 2-oxoglutarate dehydrogenase (OGDH) activity in synaptic and nonsynaptic mitochondria from rat brain were examined. In control conditions, V max and K m for 2-oxoglutaric acid (2-OG) were higher in the synaptic than in nonsynaptic mitochondria by about 45 and 55%, respectively. A particularly high sensitivity of OGDH to ammonium ions in vitro was observed in nonsynaptic mitochondria, as manifested by a 30% decrease of V max and a 60% decrease of K m for 2-OG. Synaptic mitochondria showed a slight response to HE which was manifested by a 12% increase of V max . In nonsynaptic mitochondria a 19% decrease of K m for 2-OG was observed, but V max was unaffected. Nonsynaptic mitochondria from HE rats reacted to the addition of ammonium ions in vitro with a 30% inhibition of V max but with no alteration of K m for 2-OG. In synaptic mitochondria from HE rats there was a slight inhibition of V max , but an about 15% decrease of K m for 2-OG. Based on these results, the different responses of OGDH in two mitochondrial populations to HE and ammonium ions in vitro would appear to be due to intrinsic differences between the properties of the enzyme in the synaptic and nonsynaptic brain compartments.