Figure 1

Zebrafish uricase is highly conserved. (A) Schematic illustrating amino acid conservation between zebrafish Uox with urate oxidases from other fish species (common carp (Cyprinus carpio carpio), Atlantic salmon (Salmo salar)), rodents (mouse (Mus musculus) and rat (Rattus norvegicus)), tropical clawed frog (Xenopus tropicalis), dog (Canis lupus familiaris), pig (Sus scrofa), primates (macaque (Macaca mulatta), gorilla (Gorilla gorilla gorilla), chimpanzee (Pan troglodytes), human (Homo sapiens)) and Drosophila melanogaster (percentages show amino acid conservation with zebrafish Uox). Alignment columns with no gaps are coloured in blue and violet. Violet colour indicates highly conserved regions (same residue in all alignment rows) and blue indicates less conserved regions. Unaligned residues are shown in grey. (B) Phylogenetic analysis of zebrafish Uox using BLASTP and the neighbour joining method with a Grishin distance model. Species lacking a functional uricase protein are highlighted in red. (C) Schematic illustrating urate metabolism in humans (that lack a functional urate oxidase (uricase) protein) and the contribution of hyperuricemia to MSU crystal formation. Purines are catabolized in the liver to urate, which is further degraded into allantoin in the presence of a functional uricase protein. Higher primates (including humans) lack a functional uricase making them sensitive to developing hyperuricemia, a risk factor for MSU crystal deposition and gout. Due to its water-insoluble properties, excess urate from the excretory pathway (kidney and intestines) is released back into the blood stream.