Hexokinase 1 and Hexokinase 2 (HK1, HK2)

Hexokinase 1 and 2 are enzymes that mediate the phosphorylation of glucose to glucose 6-phosphate, a key early step in glucose metabolism. Hexokinase 1 is widely expressed and especially abundant in brain, while Hexokinase 2 is predominant in skeletal muscle and is overexpressed in many cancers. Both isoforms associate with the outer mitochondrial membrane, binding to voltage-dependent anion channels (VDAC), which couples glycolysis to mitochondrial metabolism and confers resistance to cell death. HK2 is implicated in cancer cell survival via enhanced glycolysis (Warburg effect) and inhibition of apoptosis, making it a promising target for cancer therapy. HK1 additionally plays a role in immune cell function and inflammation, acting as a pattern recognition receptor. Drug targeting of hexokinase isoforms focuses on blocking glycolytic flux or disrupting their mitochondrial interactions, with potential applicability in cancer, neurodegeneration, and metabolic diseases.

Other names

Hexokinase type IBrain form hexokinaseHexokinase-AHexokinase BHK2

Inhibition of glucose phosphorylation (glycolysis blockade arrests cell proliferation and can induce cell death in cancer cells); Disruption of enzyme-mitochondria interaction (facilitates apoptosis in tumor cells); Reduction of ATP production (limits cell energy metabolism)