## Mycophenolate Mofetil: Selective Lymphocyte Inhibition ### Mechanism of Action **Key Point:** Mycophenolate mofetil (MMF) is a selective inhibitor of **inosine monophosphate dehydrogenase (IMPDH)**, an enzyme critical for guanine nucleotide synthesis in lymphocytes. 1. MMF is a prodrug that is rapidly hydrolyzed to **mycophenolic acid (MPA)** 2. MPA inhibits **IMPDH type II**, the predominant isoform in T and B lymphocytes 3. Depletion of guanosine nucleotides prevents lymphocyte proliferation 4. Other cell types (fibroblasts, endothelial cells) express IMPDH type I and are less affected 5. This results in **selective immunosuppression** with fewer effects on other tissues ### Why Selective for Lymphocytes? | Cell Type | IMPDH Isoform | Effect of MPA | | --- | --- | --- | | **T lymphocytes** | Type II (predominant) | Strongly inhibited | | **B lymphocytes** | Type II (predominant) | Strongly inhibited | | **Fibroblasts** | Type I | Minimally affected | | **Endothelial cells** | Type I | Minimally affected | | **Other tissues** | Type I | Minimally affected | **High-Yield:** MMF is commonly used in **organ transplantation** (renal, cardiac, hepatic) and **autoimmune diseases** (lupus nephritis, vasculitis) because of its selective lymphocyte targeting and favorable side effect profile compared to azathioprine. **Clinical Pearl:** Mycophenolate mofetil is **teratogenic** (Category D) and is contraindicated in pregnancy. Women of childbearing age must use effective contraception. **Mnemonic:** **IMPDH = I Make Purines (Deoxyribose Hypoxanthine)** — MMF blocks this enzyme to prevent lymphocyte purine synthesis.
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