XDH-1 inactivation causes xanthine stone formation in Caenorhabditis elegans which is inhibited by SULP-4-mediated anion exchange in the excretory cell.

ABSTRACT: Xanthine dehydrogenase (XDH) is a molybdenum cofactor (Moco) requiring enzyme that catabolizes hypoxanthine into xanthine and xanthine into uric acid, the final steps in purine catabolism. Human patients with mutations in XDH develop xanthinuria which can lead to xanthine stones in the kidney, recurrent urinary tract infections, and renal failure. Currently, there are no therapies for treating human XDH deficiency. Thus, understanding mechanisms that maintain purine homeostasis is an important goal of human health. Here, we used the nematode Caenorhabditis elegans to model human XDH deficiency using two clinically relevant paradigms: Moco deficiency or loss-of-function mutations in xdh-1, the C. elegans ortholog of XDH. Both Moco deficiency and xdh-1 loss of function caused the formation o

SUBMITTER: Snoozy J 

PROVIDER: S-EPMC12479013 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature