GUK1 belongs to the guanylate kinase family and typically occurs as a monomer . The enzyme’s primary function is to catalyze the ATP-dependent conversion of GMP to GDP, which is essential for maintaining the supply of guanine nucleotides necessary for various cellular processes, including signal transduction pathways . This catalytic activity is vital for the regulation of guanine nucleotide levels within the cell.
GUK1 is involved in the metabolism of cyclic GMP (cGMP) in photoreceptors, indicating its importance in visual processes . Additionally, GUK1 is essential for converting prodrugs used in cancer and viral infection treatments into their pharmacologically active metabolites. Notable examples include acyclovir, ganciclovir, and 6-thioguanine, as well as its closely related analog 6-mercaptopurine .
The GUK1 enzyme is considered a potential target for cancer chemotherapy due to its role in nucleotide metabolism . Its involvement in the activation of certain prodrugs highlights its therapeutic importance. Furthermore, mutations or dysregulation of the GUK1 gene have been associated with various diseases, including rhizomelic chondrodysplasia punctate type 4 and sarcomatous intrahepatic cholangiocarcinoma .
Research on GUK1 has provided insights into its function and potential therapeutic applications. The enzyme’s ability to convert prodrugs into active metabolites has made it a focal point in the development of treatments for cancer and viral infections . Additionally, understanding GUK1’s role in nucleotide metabolism can contribute to the development of targeted therapies for diseases associated with nucleotide dysregulation.