Amido PRTase

In leukemia cells treated with methotrexate, levels of dTTP decrease, and there may be less marked decreases in dATP and dGTP resulting from inhibition of amido PRTase. The consequent imbalance in nucleotide pools results in genetic miscoding and cell death. 

The 6-mercaptopurine 5 -monophosphate (MP-MP) formed is a potent inhibitor of amido PRTase, and thus de novo purine biosynthesis (Fig. 15-16) is blocked. The 6-mercaptodeoxy GTP (MdGTP) is incorporated into DNA and causes genetic miscoding. 

In some diseases, excessive amounts of purines are produced in the body, leading to accumulation of urate. Patients with Lesch-Nyhan syndrome lack the enzyme hypoxanthine-guanine phosphoribosyltransferase (HG-PRTase). Children born with this disorder are mentally retarded and prone to self-mutilation. They produce excessive amounts of purines due to accumulation of P-Rib-PP which stimulates the first enzyme of the pathway, amido PRTase (Fig. 15-16). The excess purines are degraded via the reactions... 

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