Glucokinase/Hexokinase-4 Human Recombinant
Hexokinase-4 Human Recombinant, Active
GCK Human Recombinant produced in E.Coli is a single, non-glycosylated polypeptide chain containing 485 amino acids (1-465 a.a) and having a molecular mass of 54.3kDa. GCK is fused to a 20 amino acid His-tag at N-terminus & purified by proprietary chromatographic techniques.
Hexokinase-1 Human Recombinant
Hexokinase-2 Human Recombinant
Hexokinase-3 Human Recombinant
Hexokinase is an enzyme that catalyzes the phosphorylation of hexoses (six-carbon sugars), primarily glucose, to form hexose phosphate. This reaction is the first step in the glycolytic pathway, which is crucial for cellular energy production. Hexokinases are classified into four main types in mammals: Hexokinase I, II, III, and IV (also known as glucokinase) .
Hexokinases exhibit distinct biological properties, including their expression patterns and tissue distribution. Hexokinase I is ubiquitously expressed in all mammalian tissues and is considered a “housekeeping enzyme.” Hexokinase II is the principal regulated isoform in many cell types and is often upregulated in cancer cells. Hexokinase III is less well understood but is known to be inhibited by glucose at physiological concentrations. Hexokinase IV, or glucokinase, is primarily found in the liver and pancreatic beta cells, where it plays a key role in glucose sensing and regulation .
The primary function of hexokinase is to phosphorylate glucose to glucose-6-phosphate, trapping glucose within the cell and committing it to the glycolytic pathway. This is essential for cellular metabolism and energy production. Hexokinase also plays a role in immune responses and pathogen recognition by contributing to metabolic flexibility, stress response, and morphogenesis, which are crucial for the virulence of certain pathogens like Candida albicans .
Hexokinase interacts with other molecules and cells through various mechanisms. It binds to the outer mitochondrial membrane via interaction with the protein porin, facilitating the use of intramitochondrial ATP for glucose phosphorylation. This proximity ensures efficient coordination between glycolysis and oxidative phosphorylation. Hexokinase undergoes an induced-fit conformational change upon binding to glucose, which prevents ATP hydrolysis and ensures efficient phosphorylation. It is also allosterically inhibited by its product, glucose-6-phosphate, which regulates the influx of glucose into the glycolytic pathway .
The expression and activity of hexokinase are tightly regulated through various mechanisms. Hexokinase isozymes are differentially expressed in tissues, allowing for tissue-specific regulation of glucose metabolism. Hexokinase I, II, and III are allosterically inhibited by glucose-6-phosphate, while Hexokinase IV (glucokinase) is regulated by insulin. Post-translational modifications, such as phosphorylation, also play a role in modulating hexokinase activity. Additionally, transcriptional regulation by hormones like insulin ensures that hexokinase levels are adjusted according to the body’s metabolic needs .
Hexokinase has several applications in biomedical research, diagnostics, and therapeutic strategies. It is used in glucose assays to measure blood glucose levels, which are crucial for diagnosing and managing diabetes. Hexokinase inhibitors are being explored as potential cancer therapies, given the enzyme’s role in the enhanced glycolysis observed in cancer cells. Additionally, hexokinase’s involvement in glucose sensing makes it a target for developing treatments for metabolic disorders .
Hexokinase plays a vital role throughout the life cycle, from development to aging and disease. During development, hexokinase activity is crucial for providing the energy needed for cell growth and differentiation. In adulthood, hexokinase helps maintain metabolic homeostasis and energy production. In aging and disease, alterations in hexokinase expression and activity can contribute to metabolic disorders, cancer, and other age-related diseases. The enzyme’s ability to sense and respond to changes in glucose levels ensures that cells can adapt to varying metabolic demands throughout the life cycle .