Brain metabolism of branched-chain amino acids

Abstract

The synthesis of brain glutamate requires an amino group donor that is efficiently transported into the brain and that is readily transaminated. The branched-chain amino acids (BCAA), particularly leucine, play this important role. The uptake of leucine across the blood-brain barrier is faster than any other amino acid. Studies with 15N-labelled branched-chain amino acids indicate that at least one third of the amino groups of brain glutamate are derived from the BCAA; leucine alone probably donates at least 25%. Transamination occurs in large measure in astrocytes, which articulate closely with the brain capillaries across which amino acids must past as they are transported from the blood. After using BCAA nitrogen for glutamate synthesis, the astrocytes may release the branched-chain ketoacid, e.g., alpha-ketoisocaproate, to the extracellular fluid, from which it can be taken up in a neuronal compartment and there converted back to leucine. This process, which consumes an equimolar amount of glutamic acid, may provide a mechanism for the "buffering" of brain glutamate if levels of this excitatory (and potentially toxic) neurotransmitter become elevated. Leucine so formed in neurons is released to the extracellular fluid and transported back to the astrocytes, thereby completing a "leucine-glutamate cycle."