Hexokinase-1 (HK1)

Hexokinase-1 (HK1) is a ubiquitous enzyme that catalyzes the first and rate-limiting step of glucose metabolism, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. Primarily localized to the outer mitochondrial membrane through its interaction with the voltage-dependent anion channel 1 (VDAC1), HK1 facilitates the coupling of glycolysis with mitochondrial oxidative phosphorylation to efficiently meet cellular energy demands. Beyond its metabolic role, HK1 serves as a pattern recognition receptor for bacterial peptidoglycan, modulating the innate immune response and the NLRP3 inflammasome. It also possesses anti-apoptotic properties by stabilizing mitochondrial membrane potential and preventing the release of pro-apoptotic factors. Mutations in the HK1 gene are linked to diverse clinical conditions, including hereditary non-spherocytic hemolytic anemia, Charcot-Marie-Tooth disease, and neurodevelopmental disorders. In oncology, HK1 is frequently overexpressed in various cancers, supporting the Warburg effect and tumor survival, making it a significant focus for metabolic-targeted therapeutic development.

Other names

Hexokinase type IHK IHexokinase-ABrain form hexokinaseHKDHXK1RP79HMSNRNEDVIBA

Competitive inhibition of glucose binding, ATP-competitive inhibition, disruption of mitochondrial binding, and feedback inhibition by glucose-6-phosphate analogs.