Figure 113

Mechanism of immunosuppression of azathioprine and mycophenolate mofetil (MMF). Azathioprine and MMF prevent lymphocyte proliferation by way of inhibition of purine base synthesis, thus resulting in decreased production of the building blocks of nucleic acids (ie, DNA and RNA). Azathioprine is metabolized to 6-mercap-topurine (6-MP), which is further converted to 6-ionosine monophosphate. This molecule inhibits key enzymes in the de novo pathway of purine synthesis (adenosine monophosphate [AMP] and guanosine monophosphate [GMP]). MMF is metabolized to mycophenolic acid, which is a non-competitive inhibitor of the enzyme that converts inosine monophosphate (IMP) to GMP. The depletion of GMP may have effects other than inhibition of nucleic acid production. Some events of T-lymphocyte activation are independent of guanosine triphosphate (GTP), as is the assembling of certain adhesion molecules. ATP—adenosine triphosphate; HGPRT—hypoxanthine-gua-nine phosphoribosyl transferase; IMPD— inosine-monophosphate dehydrogenase; PRPP—phosphoribosyl pyrophosphate; 6-m-MP—6-methyl-mercaptopurine; TIMP— thioinosine monophosphate. (Adapted from de Mattos and coworkers [3,4].)

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