Phosphoribosylpyrophosphate, effect

When injected, azathioprine (Imuran) is rapidly converted to 6-mercaptopurine. The half-life of azathioprine after intravenous injection is 10 to 20 min, and that of 6-mercaptopurine is somewhat longer. The cytotoxic activity of these thiopurines is due to the conversion of mercaptopurine to 6-thiouric acid, a noncarcinostatic metabolite. This action is thought to block the excess synthesis of inosinic acid from its precursors, glutamine and phosphoribosylpyrophosphate. In addition, unlike cyclophosphamide, azathioprine is a potent anti-inflammatory substance that can cause a reduction in the number of monocytes and neutrophils at inflammatory sites. Antibody responses are also inhibited by azathioprine. Studies in humans have shown that azathioprine decreases the y-globulin and antibody levels, thus influencing IgG rather than IgM production. This makes azathioprine an effective immunosuppressant in the early phases of immune responses. It is less effective or completely ineffective in altering either the effector phase or already established reactivities. 

Nierlich, D.P. and Magasanik, B. 1965. Regulation of purine ribonucleotide synthesis by end product inhibition The effect of adenine and guanine ribonucleotides on the 5 -phosphoribosylpyrophosphate amidotransferase in Aerobacter aerogenes. J. 

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