Hexokinase 3 (HK3) (HK3)

Hexokinase 3 (HK3) is a key enzyme in the glycolytic pathway, catalyzing the ATP-dependent phosphorylation of glucose to glucose-6-phosphate [UniProt P52790]. It is distinguished from other hexokinase isoforms by its high affinity for glucose and its susceptibility to substrate inhibition at high glucose concentrations [PubMed 24610836]. HK3 is primarily expressed in myeloid cells, such as neutrophils and monocytes, and its expression is often used as a marker for myeloid differentiation [NCBI Gene 3099]. In various malignancies, including acute myeloid leukemia and certain solid tumors, HK3 is upregulated to support the increased metabolic demands of rapidly proliferating cells [PubMed 30217980]. The enzyme also plays a role in cytoprotection, helping cells survive under conditions of oxidative stress or hypoxia [PubMed 21832034]. While specific inhibitors for the HK3 isoform are not yet clinically available, broad-spectrum hexokinase inhibitors like 2-deoxy-D-glucose and lonidamine are used to study its therapeutic potential [PubChem]. Targeting HK3 mRNA via antisense oligonucleotides or RNA interference represents a potential strategy to selectively reduce its expression in cancer cells [PubMed 24610836]. However, the high sequence homology between hexokinase isoforms poses a significant challenge for developing selective small-molecule inhibitors. Furthermore, because of its role in normal myeloid function, therapeutic targeting of HK3 must be carefully managed to avoid potential immune-related side effects. Overall, HK3 serves as both a metabolic target and a potential biomarker for disease progression and treatment response in oncology.

Other names

HKIIIHexokinase type IIIHK 3

Inhibition of the ATP-dependent phosphorylation of glucose to glucose-6-phosphate, the rate-limiting first step of glycolysis.