PRKAA1 and brain neoplasm: Our study strongly demonstrates that GBM exhibits metabolic dependency in glucose-derived de novo serine biosynthesis to overcome serine/glycine-defective brain microenvironmental stress, and our data defines the central role of ROS-AMPK-HIF-1α signaling in regulating the glucose-derived de novo serine biosynthesis to support the proliferation and survival of GBM cells and brain tumor growth under the limited serine and glycine of the brain microenvironment.