2015 Antineoplastics


Review of purine synthesis

Pseudofeedback inhibitionFive critical components:

  1. The souce of ribose is 5-phosphoribosyl-1-pyrophosphate (PRPP). Synthesis of PRPP is catalyzed by purine nucleoside phosphorylase (PNP).

  2. The first committed step in purine synthesis is the formation of 5-phosphoribosylamine via the enzyme PRPP glutamylamidotransferase.

  3. 6-MP and 6-TG enter via the "salvage pathway" where PRPP reacts with hypoxanthine or guanine bases to form IMP or GMP, respectively. This reaction is catalyzed by hypoxanthine-guanine phosphoribosyl transferase (HGPRT).

  4. GMP is converted to GDP by guanylyl kinase. This is the step that is blocked by 6-MP and 6-TG, causing a buildup of GMP.

  5. There are numerous negative feedback pathways mediated by increased concentrations of GMP. The most critical is the inhibition of the first two steps in the purine biosynthetic pathway (ribose-5-phosphate PRPP 5-phosphoribosylamine). 6-MP and 6-TG therefore shut down purine sythesis by limiting both the neosysnthesis and salvage pathways.

Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM