Studies on metabolism of branched chain amino acids in brain and other tissues of rat with special reference to leucine.

Leucine aminotransferase (EC 2.6.1.6) and 2-oxoisocaproate dehydrogenase (EC 1.2.4.3) were studied in rat cerebral cortex, cerebellum, brain stem, liver, and muscle in normal and animals starved for 48 hours. In the brain, leucine aminotransferase, valine aminotransferase, and 2-oxoisocaproate dehydrogenase showed a significant increase in starvation only in cerebellum while there was increase in 2-oxoisocaproate dehydrogenase in cerebral cortex only. A significantly high increase in the activity of 2-oxoisocaproate dehydrogenase was observed in muscle in starvation. A significant decrease in the activity of leucine aminotransferase was observed in liver in starvation. The increase in the activity of 2-oxoisocaproate dehydrogenase in muscle and a decrease in the activity of leucine aminotransferase in liver in starvation indicate that the leucine is predominantly metabolized in extra hepatic tissues particularly in muscle. As a result of intraperitoneal administration of 2 ml of leucine (5 mM), a significant increase in 2-oxoisocaproate dehydrogenase occurred in cerebral cortex, liver, and muscle while a profound increase in the activity of glutamate dehydrogenase (EC 1.4.1.2) was observed in all the brain regions and liver under these conditions. A significant increase in the content of glutamic acid, alanine, and GABA was observed in all the three regions of the brain after the administration of leucine. A significant increase in the content of glutamine was observed only in the cerebellum and cerebral cortex after leucine administration. These results indicate that leucine in brain might contribute to the formation of glutamate, not only by transamination, but also by promoting glutamate dehydrogenase activity. Thus, there is a change in the metabolism of glutamate family of amino acids and energy depletion. These results are discussed in relation to the brain function.