Glutamate oxaloacetate transaminase 2, a mitochondrial enzyme, catalyzes the conversion of oxaloacetate to aspartate. Studies show that the metabolite pyridoxal phosphate is selectively required by acute myeloid leukemia. PLP-dependent GOT2 selectively sustains leukemic cell proliferation. Depletion of GOT2 suppresses the proliferation of acute myeloid leukemia cells. In addition, mouse hematopoietic stem cells are dependent on cell-autonomous aspartate synthesis. Got2 deletion leads to decreased aspartate levels and reduced hematopoietic stem cell function. Furthermore, GOT2-dependent aspartate synthesis is also necessary for protein and collagen biosynthesis in chondrocytes and is critical for chondrocyte proliferation and growth.
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