Reprogramming of amino acid metabolism in cholangiocarcinoma: A potential target for metabolic-targeted therapy

Figure 1 The alteration of glutamine metabolism in cholangiocarcinoma cells. Glutaminolysis begins with the transportation of glutamine through the inner mitochondrial membrane through solute carrier family 1 member 5, followed by the conversion of glutamine to glutamate by GLSs. Mitochondrial glutamate can be converted to alpha-ketoglutarate by GDH1. Aspartate can be exported to the cytoplasm, undergo transamination, and converted to oxaloacetate by glutamate-oxaloacetate transaminase (GOT1). Annexin A1 generally functions as a scaffold protein, connecting ubiquitin-specific protease 5 with GOT1 and facilitating their interaction. This scaffolding activity promotes GOT1 deubiquitylation and stabilization, inhibiting its degradation via the ubiquitin-proteasome pathway. SLC1A5: Solute carrier family 1 member 5; AGC: Aspartate-glutamate carrier; GLS1: Glutaminase 1; GDH: Glutamate dehydrogenase; GOT: Glutamic-oxaloacetic transaminase; α-KG: Alpha-ketoglutarate; ANXA1: Annexin A1; USP5: Ubiquitin-specific protease 5; GAD1: Glutamate decarboxylase 1; SLC25A11: Solute carrier family 25 member 11; TCA: Tricarboxylic acid.