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Branched chain amino acid transaminases in brain in methionine sulphoximine (MSI) toxicity
1School of Life Sciences, University of Hyderabad, India.
Abstract:
The effect of intraperitoneal administration of L-methionine-DL-sulphoximine (MSI) was studied on branched-chain amino acid transaminases (BCAA-T) in different regions of rat brain and in liver. Administration of an acute dose of MSI (300 mg/kg body weight) resulted in a significant decrease in leucine aminotransferase activity in cerebral cortex, cerebellum, and brain-stem, while the activity of isoleucine aminotransferase was enhanced in hippocampus, corpus striatum, brain stem, and midbrain. Activities of both these enzymes changed marginally or remained unaltered in other regions of the brain. Valine aminotransferase showed a significant decrease in all the regions of the brain except in cerebellum. Following the administration of a sub-acute dose of MSI (150 mg/kg body wt.), the activities of the three BCAA aminotransferases were found to be enhanced in all regions of the brain. The results are discussed in relation to the utilization of BCAA for the production of glutamate and glutamine in hyperammonemia.
Insights
L-methionine-DL-sulphoximine (MSI) alters branched-chain amino acid transaminases (BCAA-T) in rat brains. Acute MSI decreased some BCAA-T activities, while sub-acute doses increased them across brain regions.
Area of Science:
- Neurochemistry
- Enzymology
- Toxicology
Background:
- Branched-chain amino acids (BCAAs) are crucial for neurotransmitter synthesis.
- Hyperammonemia affects brain amino acid metabolism.
- L-methionine-DL-sulphoximine (MSI) is a known modulator of amino acid metabolism.
Purpose of the Study:
- To investigate the impact of L-methionine-DL-sulphoximine (MSI) on branched-chain amino acid transaminases (BCAA-T) in various rat brain regions and the liver.
- To understand how different doses of MSI affect the activity of leucine, isoleucine, and valine aminotransferases.
- To explore the implications of these enzymatic changes in the context of hyperammonemia and BCAA utilization for glutamate and glutamine production.
Main Methods:
- Intraperitoneal administration of L-methionine-DL-sulphoximine (MSI) to rats.
- Assay of branched-chain amino acid transaminase (BCAA-T) activities, specifically leucine, isoleucine, and valine aminotransferases.
- Analysis of enzyme activity in different brain regions (cerebral cortex, cerebellum, brain-stem, hippocampus, corpus striatum, midbrain) and liver.
- Comparison of effects from acute (300 mg/kg) and sub-acute (150 mg/kg) MSI doses.
Main Results:
- Acute MSI administration (300 mg/kg) significantly decreased leucine aminotransferase in the cerebral cortex, cerebellum, and brain-stem.
- Isoleucine aminotransferase activity increased in the hippocampus, corpus striatum, brain stem, and midbrain following acute MSI.
- Valine aminotransferase decreased in most brain regions, except the cerebellum, after acute MSI.
- Sub-acute MSI administration (150 mg/kg) led to enhanced activities of all three BCAA-T enzymes in all brain regions.
Conclusions:
- MSI exerts differential effects on BCAA-T activities in specific brain regions, with acute doses showing varied impacts and sub-acute doses generally increasing enzyme activity.
- The observed alterations in BCAA-T suggest a complex modulation of BCAA metabolism by MSI.
- These findings provide insights into BCAA utilization for glutamate and glutamine synthesis, particularly relevant in hyperammonemic conditions.