MECHANISM OF ACTION-
1. Mercaptopurine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase).
2. Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) convertes mercaptopurine to thioinosinic acid (TIMP).
3. This intracellular nucleotide inhibits several reactions involving inosinic acid (IMP) like, the conversion of IMP to xanthylic acid (XMP) and also the conversion of IMP to adenylic acid (AMP) via adenylosuccinate (SAMP).
4. In addition, 6-methylthioinosinate (MTIMP) is formed through the methylation of TIMP.
5. Both TIMP and MTIMP has found to inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase, which is the first enzyme unique to the de novo pathway for purine ribonucleotide synthesis.
4. Experimentally it is known that radiolabeled mercaptopurine may be recovered from the DNA in the form of deoxythioguanosine.
5. Some mercaptopurine is converted to nucleotide which is the derivatives of 6-thioguanine (6-TG) by the sequential actions of inosinate (IMP) dehydrogenase and xanthylate (XMP) aminase, converting TIMP to thioguanylic acid (TGMP).