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).
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