Metabolism of BCAAs

Abstract

The three branched chain amino acids are unique in that the first catabolic step does not occur in the liver. Leucine, isoleucine, and valine share the first two catabolic enzymes—branched chain aminotransferase (BCAT) and branched chain ketoacid dehydrogenase (BCKD). Both BCAT isoforms use Vitamin B-6 cofactors as temporary acceptors of the α-amino group during the process of aminating α-ketoglutarate, which becomes glutamate. The deaminated BCAAs are known as BCKAs, and can be reaminated into their BCAA form. The next step in BCAA catabolism, the decarboxylation of the BCKAs, is irreversible. In some tissues, the mitochondrial isoform of BCAT (BCATm), appears to form a metabolon with BCKD, which is a physical relationship between the BCATm enzyme and the BCKD enzyme complex. This facilitates the transfer of substrates and increases the efficiency of the reactions. After decarboxylation of the BCKA, the catabolic pathways for the three BCAA precursors diverge, utilizing different enzymes and processes. Disruptions in BCAA metabolism, primarily occurring in the first two steps, can cause a number of severe metabolic disorders. Additionally, changes in both BCAAs and BCAA enzymes have been implicated in the pathophysiology of TBI.