Bookshelf

Two types of GTP synthesis pathways. GTP synthesis is controlled by two pathways. A sugar, phosphoribosyl diphosphate (PRPP), is made by ribose-5-phosphate (R5P) involved in pentose phosphate pathway. In de novo pathway, IMP is generated from PRPP through high nutrient and energy consuming reactions. On the other hand, salvage pathway produces a new IMP or GMP by directly connecting a sugar (PRPP) and a nucleobase (hypoxanthine or guanine). These nucleobases come from recycled IMP or GMP metabolites (inosine or guanosine). This economical pathway is favored in adult tissues. IMP dehydrogenase (IMPDH) oxidizes IMP to XMP. IMPDH is involved in the first step of guanine nucleotide synthesis and plays important roles in proliferation, cellular homeostasis, and also tumors facilitation including GBM. IMPDH activity is strongly inhibited by mycophenolate mofetil (MMF), which is a precursor of mycophenolic acid (MPA) and uses as prodrug of immunosuppressant. ATP, adenosine triphosphate; GDP, guanosine diphosphate; GMP, guanosine monophosphate; GTP, guanosine triphosphate; IMP, inosine monophosphate; IMPDH, IMP dehydrogenase; MMF, mycophenolate mofetil; MPA, mycophenolic acid; PRPP, phosphoribosyl diphosphate; R5P, ribose-5-phosphate; XMP, xanthine monophosphate.