Biological systems phosphate-metabolizing inhibition

Azathioprine is a cytotoxic inhibitor of purine synthesis effective for the control of tissue rejection in organ transplantation. It is also used in the treatment of autoimmune diseases. Its biologically active metabolite, mercaptopurine, is an inhibitor of DNA synthesis. Mercaptopurine undergoes further metabolism to the active antitumour and immunosuppressive thioinosinic acid. This inhibits the conversion of purines to the corresponding phosphoribosyl-5 phosphates and hypoxanthine to inosinic acid, leading to inhibition of cell division and this is the mechanism of the immunosuppression by azathioprine and mercaptopurine. Humans are more sensitive than other species to the toxic effects of the thiopurines, in particular those involving the haematopoietic system. The major limiting toxicity of the thiopurines is bone marrow suppression, with leucopenia and thrombocytopenia. Liver toxicity is another common toxic effect. 

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