Figure 2.

BCAA and Glutamine metabolism. BCAAs such as leucine, isoleucine, and valine are imported into the cell by high affinity transporters such as LAT-1. Branched chain amino acid transaminases (BCAT) catalyze the highly reversible transfer of α-amino groups from any BCAA to α-ketogluterate (αKG) to generate glutamate. More glutamate can be synthesized by the action of mitochondrial glutaminase (GLS) on glutamine imported into the cell via the alanine/serine/cysteine transporter (ASCT2, which is capable of high affinity glutamine transport). Glutamate is converted to αKG by either glutamate dehydrogenase (GDH) or several amino acid transaminases (TAs) such aspartate aminotransferase (AST) or alanine transaminase (ALT). αKG produced in this way is anaplerotic to the tricarboxylic acid (TCA) cycle. αKG can be reversibly converted to citrate via isocitrate dehydrogenase (IDH) which is overexpressed in some AMLs. AMLs bearing IDH mutations produce excess 2-hydroxygluterate (R-2HG) which can inhibit BCAT activity. All other specific enzyme inhibitors (highlighted in red) are discussed in the main text.