There are several features of the metabolism of the indispensable BCAAs that set them apart from other indispensable amino acids. BCAA catabolism involves 2 initial enzymatic steps that are common to all 3 BCAAs; therefore, the dietary intake of an individual BCAA impacts on the catabolism of all 3. The first step is reversible transamination followed by irreversible oxidative decarboxylation of the branched-chain alpha-keto acid transamination products, the branched chain alpha-keto acids (BCKAs). The BCAA catabolic enzymes are distributed widely in body tissues and, with the exception of the nervous system, all reactions occur in the mitochondria of the cell. Transamination provides a mechanism for dispersing BCAA nitrogen according to the tissue's requirements for glutamate and other dispensable amino acids. The intracellular compartmentalization of the branched-chain aminotransferase isozymes (mitochondrial branched-chain aminotransferase, cytosolic branched-chain aminotransferase) impacts on intra- and interorgan exchange of BCAA metabolites, nitrogen cycling, and net nitrogen transfer. BCAAs play an important role in brain neurotransmitter synthesis. Moreover, a dysregulation of the BCAA catabolic pathways that leads to excess BCAAs and their derivatives (e.g., BCKAs) results in neural dysfunction. The relatively low activity of catabolic enzymes in primates relative to the rat may make the human more susceptible to excess BCAA intake. It is hypothesized that the symptoms of excess intake would mimic the neurological symptoms of hereditary diseases of BCAA metabolism.