• The role of Hexokinase Enzymes in Liver Cancer Metabolism
  • Dr. Dariush Norouzian,1,* Paniz Mahmoudi,2 Dr. Mohmmad Mahdi Eslami,3 Dr. Reza Mirlohi,4
    2. Islamic Azad University Tehran Medical sciences
    3. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran
    4. Member of the Bioinformatics Research Group, Nasim Research Institute, Tehran, Iran


  • Introduction: Liver cancer is the sixth most commonly diagnosed cancer and the third most common cause of cancer death. The liver, as a major metabolic organ, plays a crucial role in regulating body metabolism and the metabolism of glucose, fats, and amino acids. Cancer cells, even in the presence of oxygen, switch from normal metabolism to aerobic glycolysis or the Warburg effect, where they convert glucose into lactate.This process is controlled by hexokinase (HK) enzymes. The goal of this study is to examine the role of hexokinase and the impact of carbohydrates on liver metabolism, and to compare the function of hexokinases in healthy and cancerous cells using bioinformatic data.
  • Methods: In this study, we used meta-analysis and bioinformatics methods. The Mega Gene software program were used for analysis, while Swiss Dock was used for protein-ligand docking and Clus Pro for protein-protein docking. The 3D structures of the proteins for docking were also obtained from the PDB website.
  • Results: HKDC1 protein, under hypoxic conditions, promotes the stemness of hepatocellular cancinoma (HCC) by binding to GSK3 BETA and stabilizing the beta-catenin protein. Additionally, it was also found that 3-BrPA causes a chemical modification of the HKII protein through a covalent bond, which inhibits its enzymatic activity and triggers its dissociation from mitochondria, ultimately leading to cell death. This chemical modification is dependent on a specific conformation of the HKII protein.
  • Conclusion: This study demonstrates the importance of hexokinase enzymes in liver cancer. HKDC1 plays a critical role in promoting metastasis in liver cancer, making it a promising therapeutic target for advanced disease.Additionally, the dissociation of HKII from mitochondria induces cancer cell death, highlighting potential pathways for intervention.
  • Keywords: Hexokinases, 3BrPA, Warburg effect, GSK3B , HKDC1 protein .