Human Uricase Loss: An Evolutionary Gain Against Disease

The peroxisomal enzyme uricase (urate: oxygen oxidoreductase E.C. 1.7.3.3.) is a tetramer of 32 kD subunits (1-4) that catalyzes the oxidation of uric acid to allantoin during purine metabolism. This enzyme has been found in liver homogenates of most vertebrates (fish, amphibian and mammalian species) but is absent in hominoids (gibbons, orangutans, chimpanzees, gorillas and man) (5). A common evolutionary origin for all uricases is suggested by the evidence depicted in Table 1, however previous attempts to determine the homology among uricases of evolutionarly distant species have been unsuccessful. Fujiwara et al (1) demonstrated immunorecognition among amphibian uricases using an antiserum prepared against native uricase from Rana catesbeiana but were unable to detect immunological cross reaction with fish or mammalian uricases. The failure to see cross reactivity among these proteins might reflect their degree of amino acid sequence divergence (6).