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Purine metabolism: Wikis

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Many organisms have metabolic pathways to synthesize and break down purines.

Contents

Synthesis

Purines are biologically synthesized as nucleotides (bases attached to ribose 5-phosphate). The committed step is amidophosphoribosyltransferase.

Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is synthesised on a pre-existing ribose-phosphate through a complex pathway using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as formate ions transferred from the coenzyme tetrahydrofolate.

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GMP

AMP

Degradation

Purines are metabolised by several enzymes:

Guanine

Adenine

Salvage

Purines from turnover of nucleic acids (or from food) can also be salvaged and reused in new nucleotides.

Disorders

When a defective gene causes gaps to appear in the metabolic recycling process for purines and pyrimidines, these chemicals are not metabolised properly, and adults or children can suffer from any one of twenty-eight hereditary disorders, possibly some more as yet unknown. Symptoms can include gout, anaemia, autism, epilepsy, delayed development, deafness, compulsive self-biting, kidney failure or stones, or loss of immunity.

Pharmacotherapy

Modulation of purine metabolism has pharmacotherapeutic value.

Purine synthesis inhibitors inhibit the proliferation of cells, especially leukocytes. These inhibitors include azathioprine, an immunosuppressant used in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohn's disease and ulcerative colitis.

Mycophenolate mofetil is an immunosuppressant drug used to prevent rejection in organ transplantation, it inhibits purine synthesis by blocking inositol monophsophate dehydrogenase. Also Methotrexate indirectly inhibits purine synthesis by blocking the metabolism of folic acid ( it's an inhibitor of the Dihydrofolate reductase ).

Allopurinol is a drug which inhibits the enzyme xanthine oxidoreductase and thus lowers the level of uric acid in the body. This may be useful in the treatment of gout, which is a disease caused by excess uric acid forming crystals in joints.

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