Hexokinase 3 (HK3)

Hexokinase 3 (HK3) is a cytoplasmic enzyme belonging to the sugar kinase family, encoded by the HK3 gene on human chromosome 5[1]. Like other hexokinases, HK3 catalyzes the first committed step in glucose metabolism: the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. HK3 is unique among hexokinase isoforms in being predominantly expressed in myeloid cells, including granulocytes and macrophages, and is particularly upregulated during myeloid differentiation and in certain leukemias such as AML[2]. While dispensable for overall glycolytic flux in myeloid leukemic cells—unlike HK2—HK3 plays a critical non-glycolytic role in promoting cell survival, regulating apoptosis, and controlling the response to oxidative stress, in part through interaction with the proapoptotic protein BIM[2]. Elevated HK3 expression has been linked to poor prognosis in several cancers, including glioblastoma multiforme and colorectal cancer, often in association with immune and inflammatory pathways[3]. There are currently no approved drugs specifically targeting HK3, and therapeutic targeting would require caution due to possible effects on hematopoietic cell survival and function.

Other names

Hexokinase IIIHexokinase-CHK IIIHKIIIHexokinase type IIIHXK3ATP:D-hexose 6-phosphotransferasehexokinase 3 (white cell)hexokinase type IIIhexokinase-C

ATP-dependent phosphorylation of glucose to glucose-6-phosphate; modulates apoptotic and stress pathways in myeloid cells, interacts with proapoptotic protein BIM; cytoprotective function during cell differentiation/stress