Hexokinase type I (mitochondrially-bound) (HKI)

Hexokinase type I is an enzyme that catalyzes the first committed step in glucose metabolism by phosphorylating glucose to produce glucose 6-phosphate. This isozyme is distinguished by its strong association with the outer mitochondrial membrane through interaction with the voltage-dependent anion channel (VDAC or porin), which allows it to preferentially use intramitochondrial ATP as a substrate[3]. The binding of HKI to mitochondria facilitates efficient coupling between glycolysis and oxidative phosphorylation, ensuring that energy production matches cellular demand and minimizing excessive lactate formation[3]. In most tissues, especially those with high energy requirements such as brain and muscle, this localization supports catabolic functions—directing glucose into pathways for immediate ATP generation[2][3]. Unlike other isoforms such as hexokinase II—which can shuttle between cytoplasm and mitochondria—HKI remains predominantly bound to mitochondria under physiological conditions[2]. This persistent association also plays a role in regulating apoptosis; detachment from the mitochondrial membrane can trigger cell death pathways. Overexpression or dysregulation of mitochondrial hexokinases has been implicated in cancer cell survival due to their anti-apoptotic effects[2][3]. Note on interacting drugs/mechanisms/biomarkers/safety concerns: No specific drugs directly targeting mitochondrially-bound HKI are listed in these sources; however, inhibitors of general hexokinases or agents disrupting their mitochondrial binding are under investigation for cancer therapy based on their role in tumor metabolism.

Other names

Hexokinase Imitochondrial hexokinaseHK1Type I hexokinasemitochondrially-associated hexokinase