American Board of Surgery Qualifying Exam (ABS QE) Practice Test

What mechanism of action does Mycophenolate mofetil primarily utilize?

1. Inhibits cyclooxygenase

2. Inhibits calcineurin

3. Inhibits inosine monophosphate dehydrogenase

4. Inhibits interleukin production

The correct answer is: Inhibits inosine monophosphate dehydrogenase

Mycophenolate mofetil primarily exerts its effects by inhibiting inosine monophosphate dehydrogenase (IMPDH), an enzyme critical in the de novo synthesis pathway of purines. This inhibition is particularly significant because it selectively impacts lymphocytes, which are highly dependent on this pathway for their proliferation and function, especially during an immune response. By blocking IMPDH, Mycophenolate mofetil reduces the availability of purines necessary for DNA synthesis, thereby inhibiting the proliferation of T and B lymphocytes. This mechanism underlies its use as an immunosuppressant, particularly in preventing organ rejection in transplant patients and treating autoimmune diseases. In contrast, other mechanisms mentioned involve different pathways and targets. The inhibition of cyclooxygenase is related to non-steroidal anti-inflammatory drugs and impacts prostaglandin synthesis, while calcineurin inhibitors are part of the mechanism utilized by drugs like tacrolimus, which inhibit T-cell activation. The inhibition of interleukin production pertains to other immunosuppressive agents that target cytokine signaling, not Mycophenolate mofetil specifically. Thus, the precise action of Mycophenolate mofetil is primarily through the inhibition of inosine monophosphate