Question

Metabolism of purine and pyrimidine and clinical significants

Answer 1

Metabolism of purine and pyrimidine

Since purine and pyrimidine metabolism is essential in all types of cells with a variety of functions, the symptoms caused by the enzyme abnormalities are diverse. At least 30 monogenic abnormalities in purine and pyrimidine metabolism have been reported. Among the enzyme abnormalities in purine pathways, hypoxanthine guanine phosphoribosyltransferase (HGPRT) deficiency and PRPP synthetase superactivity cause hyperuricemia with or without psychological, motor and neurological abnormalities (Figure 1). Adenine phosphoribosyltransferase deficiency and type I and type II xanthine oxidase deficiencies cause urolithiasis, while ADA deficiency and purine nucleoside phosphorylase deficiency cause immunodeficiency. In adenylosuccinate lyase deficiency, ATIC deficiency and molybdenum cofactor deficiency, psychological, motor, and neurological symptoms are the main disorders, while deoxyguanosine kinase deficiency causes progressive liver damage. Thiopurine methyltransferase deficiency is of particular interest because it is associated with drug-related adverse events caused by 5-mercaptopurine, thioguanine and azathioprine. Finally, myoadenylate deaminase deficiency may cause muscle abnormalities.