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Rat cerebral mitochondrial glutaminase activity is unaffected by moderate hyperammonemia in two models
J Albrecht1, W Hilgier, L Faff
1Department of Neurotoxicology, Polish Academy of Sciences, Warsaw, Poland.
Abstract:
The phosphate-dependent (PAG) and phosphate-independent (PIndG) glutaminase activities were measured in cerebral perikaryal mitochondria derived from rats subjected to ammonium acetate- induced "simple" hyperammonemia (SHA) or thioacetamide-induced hepatic encephalopathy (HE). These two moderately hyperammonemic conditions were previously found to be accompanied by pronounced changes in virtually all the enzyme activities coupling the tricarboxylic acid cycle to the synthesis and metabolism of the excitatory neurotransmitter glutamate. Both PAG and PIndG remained unaffected by SHA or HE, indicating that they do not contribute to the cerebral glutamine/glutamate imbalance associated with both conditions.
Insights
Phosphate-dependent and phosphate-independent glutaminase activities in rat brain mitochondria did not change during hyperammonemia or hepatic encephalopathy. These enzymes are not responsible for the observed glutamate imbalance in these conditions.
Area of Science:
- Biochemistry
- Neuroscience
- Toxicology
Background:
- Hyperammonemia and hepatic encephalopathy (HE) disrupt brain function.
- These conditions are linked to altered glutamate metabolism and neurotransmission.
- Previous studies noted widespread changes in enzymes involved in the tricarboxylic acid cycle and glutamate pathways.
Purpose of the Study:
- To investigate the role of phosphate-dependent (PAG) and phosphate-independent (PIndG) glutaminase activities in hyperammonemia.
- To determine if these glutaminase activities contribute to the cerebral glutamine/glutamate imbalance in simple hyperammonemia (SHA) and HE.
Main Methods:
- Mitochondria were isolated from rat cerebral perikarya.
- Rats were subjected to ammonium acetate-induced SHA or thioacetamide-induced HE.
- Phosphate-dependent (PAG) and phosphate-independent (PIndG) glutaminase activities were measured.
Main Results:
- Both PAG and PIndG glutaminase activities remained unaffected in rats with SHA.
- PAG and PIndG glutaminase activities were also unchanged in rats with HE.
- These findings indicate no contribution of these specific glutaminase activities to the observed imbalance.
Conclusions:
- Phosphate-dependent and phosphate-independent glutaminase activities are not altered in experimental models of hyperammonemia and hepatic encephalopathy.
- These enzymes do not play a role in the cerebral glutamine/glutamate imbalance characteristic of these conditions.
- Further research is needed to identify the specific enzymes responsible for altered glutamate metabolism in hyperammonemia.