2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase (URAD)

2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase (URAD) is a carboxy-lyase enzyme responsible for the stereoselective decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) to (S)-allantoin, which is the last enzymatic step in the uric acid degradation pathway[4][9]. It is predicted to function in peroxisomes and plays a role in amide and nucleobase-containing small molecule metabolism, specifically in urate catabolism[5][8]. In humans and higher primates, URAD and other enzymes in this pathway have been pseudogenized, resulting in increased blood urate levels and susceptibility to diseases like gout[3]. Structurally, URAD forms a homodimer and utilizes histidine and glutamate residues for catalysis. Beyond metabolic roles, elevated URAD expression has been observed in wound fibroblasts, promoting cell motility and contraction essential for wound healing, suggesting potential therapeutic relevance in tissue repair[1]. Though no drugs currently target URAD, the enzyme is a proposed candidate for enzyme-based therapies to treat gout or possibly enhance wound regeneration[3][1].

Other names

Putative 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylaseURADPRHOXNBOHCU decarboxylaseParahox neighborParahox cluster neighborUreidoimidazoline (2-oxo-4-hydroxy-4-carboxy-5-) decarboxylase

Drugs or therapeutic approaches targeting URAD would act by enhancing or mimicking enzyme activity to accelerate uric acid catabolism to allantoin, potentially as an enzyme replacement for treating hyperuricemia/gout[3]