Clinical and biochemical aspects of uric acid overproduction.
Purine nucleotides are synthesized and degraded through a regulated series of reactions which end in the formation of uric acid. Increased uric acid synthesis may be the result of two major pathophysiological disorders: increased de novo purine synthesis and enhanced purine nucleotide degradation, both of which may be the result of an increased or decreased enzyme activity. In addition, some conditions and disorders associated with uric acid overproduction have been recognized as the result of increased ATP degradation or decreased synthesis of ATP. The clinical manifestations of the diseases leading to excess uric acid synthesis are heterogenous, but symptoms related to uric acid overproduction are always secondary to the precipitation of crystals in soft tissues, joints, and the kidney excretory system. In clinical practice, serum urate concentration and urinary uric acid excretion are used to assess uric acid synthesis, taking into account that a purine-rich diet can be a confounding variable. Quantification of uric acid precursors, such as adenosine, inosine, guanosine, hypoxanthine, and xanthine, in biological fluids and intracellular nucleotides has provided further insight into the metabolic disturbances underlying disorders associated with uric acid overproduction. Additional studies are necessary to define precisely the metabolic derangement in idiopathic uric acid overproduction and to assess fully the consequences of increased purine nucleotide degradation, such as free-radical formation, increased adenosine synthesis, and reduced synthesis of signal transducers.
García Puig
J
J
Division of Internal Medicine, La Paz Hospital, Universidad Autónoma, Madrid, Spain.
Mateos
F A
FA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006073:Gout / Q000378:metabolism; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D009696:Nucleic Acids / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D012268:Ribose-Phosphate Pyrophosphokinase / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism*
D009696:Nucleic Acids; D011687:Purines; D014527:Uric Acid; D000255:Adenosine Triphosphate; D007041:Hypoxanthine Phosphoribosyltransferase; D012268:Ribose-Phosphate Pyrophosphokinase