Adenylate Kinase 4 (AK4) is one of the nine known isoenzymes of adenylate kinase in humans. These enzymes play a crucial role in cellular energy homeostasis by catalyzing the reversible transfer of phosphate groups between adenine nucleotides. The reaction they facilitate is:
This reaction is vital for maintaining the balance of adenine nucleotides within the cell, which is essential for various cellular processes.
AK4 is a mitochondrial enzyme, which means it is located within the mitochondria, the powerhouse of the cell. It is involved in the regulation of energy metabolism and is particularly important under conditions of metabolic stress. AK4 helps in maintaining the cellular energy charge by ensuring a steady supply of ADP for ATP synthesis.
AK4 has been identified as a biomarker for metastasis in lung cancer. It modulates oxidative stress and stabilizes hypoxia-inducible factor 1-alpha (HIF-1α), which drives the metastasis of lung adenocarcinoma . Overexpression of AK4 has been shown to enhance the stability of HIF-1α by increasing intracellular reactive oxygen species (ROS) levels, which subsequently induces epithelial-to-mesenchymal transition (EMT) under hypoxic conditions . This makes AK4 a potential target for therapeutic interventions in metastatic lung cancer.
Recombinant AK4 refers to the enzyme that has been genetically engineered and produced in a laboratory setting, often using bacterial expression systems such as Escherichia coli. This allows for the production of large quantities of the enzyme for research and therapeutic purposes. Recombinant AK4 is typically fused with a His-tag at the N-terminus to facilitate purification through conventional chromatography techniques .
The study of AK4 and its isoenzymes has significant implications for understanding various diseases and developing new treatments. For instance, the dysregulation or mutation of adenylate kinases is linked to several medical conditions, including neurodegenerative diseases and metabolic syndromes . The ability to produce recombinant AK4 enables researchers to investigate its structure, function, and role in disease more thoroughly.