Unveiling overlooked pathways: The uric acid catabolism genes in the human genome

In hominids, including Homo sapiens, uric acid is the end product of purine catabolism. In contrast, other placental mammals further degrade uric acid to (S)-allantoin by enzymes such as urate oxidase (uricase), HIU hydrolase (HIUase), and OHCU decarboxylase. Some organisms, such as frogs and fish, hydrolyze (S)-allantoin to allantoate and eventually to (S)-ureidoglycolate and urea, while marine invertebrates convert urea to ammonium. In H. sapiens, mutations in the uricase gene led to a reduction in the selective pressure for maintaining the integrity of the genes encoding the other enzymes of the purine catabolism pathway, resulting in an accumulation of uric acid. The hyperuricemia resulting from this accumulation is associated with gout, cardiovascular disease, diabetes, and preeclampsia. Many commonly used drugs, such as aspirin, can also increase uric acid levels. Despite the apparent absence of these enzymes in H. sapiens, there appears to be production of transcripts for uricase (UOX), HIUase (URAHP), OHCU decarboxylase (URAD), and allantoicase (ALLC). While some URAHP transcripts are classified as long non-coding RNAs (lncRNAs), URAD and ALLC produce protein-coding transcripts. Given the presence of these transcripts in various tissues, we hypothesized that they may play a role in the regulation of purine catabolism and the pathogenesis of diseases associated with hyperuricemia. Here, we specifically investigate the unique aspects of purine catabolism in H. sapiens, the effects mutations of the uricase gene, and the potential regulatory role of the corresponding transcripts. These findings open new avenues for research and therapeutic approaches for the treatment of hyperuricemia and related diseases. •Mutations in the uricase gene affected the other genes of the uric acid catabolism.•Transcripts involved in the uric acid degradation may regulate purine catabolism.•HIUase (URAHP) expresses transcripts classified as long non-coding RNA.•HIUase (URAHP) expression level appears to be strongly tissue-dependent.•URAD and ALLC genes produce transcripts classified as protein coding.