Glucose transporter family and hexokinase (GLUT/HK)

The term Glucose transporter family and hexokinase refers to a functional grouping of proteins responsible for the first two critical steps of cellular glucose utilization. The glucose transporter (GLUT) family, primarily the SLC2A gene products, facilitates the diffusion of glucose across the plasma membrane, while the hexokinase (HK) family of enzymes catalyzes the phosphorylation of glucose to glucose-6-phosphate, effectively trapping it within the cell for glycolysis or glycogen synthesis (UniProt, 2023). In many pathological states, particularly oncology, these proteins are coordinately upregulated to meet the high energy demands of rapid proliferation, a phenomenon known as the Warburg effect (Vander Heiden et al., Science, 2009). This grouping is considered 'incorrect' as a single canonical target because it combines two distinct molecular classes—transporters and enzymes—which are typically targeted by different pharmacological agents. Therapeutic strategies targeting this axis include SGLT2 inhibitors for diabetes and experimental HK2 or GLUT1 inhibitors for cancer, though systemic toxicity remains a significant challenge due to the essential role of glucose metabolism in healthy tissues like the brain and red blood cells (NIH, 2024; PubChem, 2024).

Other names

Glucose uptake and phosphorylation systemGlycolytic initiation componentsGLUT and HK complex

Inhibition of glucose entry into the cell via competitive or non-competitive blockade of transporter proteins (GLUT/SGLT) and/or inhibition of the ATP-dependent phosphorylation of glucose to glucose-6-phosphate by hexokinase enzymes.