Xanthine oxidase produces uric acid; HGPRT salvages purines
Expansion
Degradation: purine nucleotides to hypoxanthine to xanthine to uric acid, the last two steps by xanthine oxidase.
Salvage: HGPRT (hypoxanthine-guanine phosphoribosyltransferase) recycles hypoxanthine and guanine back into nucleotides, which is far more energy efficient than de novo synthesis and reduces urate production.
Lesch-Nyhan syndrome: X-linked complete HGPRT deficiency. Hyperuricaemia with gout and stones from infancy, plus a striking neurological picture of choreoathetosis, spasticity, intellectual disability and compulsive self-mutilation. Partial deficiency causes gout alone.
Gout results from urate supersaturation. Humans are unusual in lacking uricase, which is why our urate levels sit close to the solubility limit.
Drug targets
- Allopurinol and febuxostat: inhibit xanthine oxidase, reducing production
- Probenecid: increases renal excretion
- Rasburicase: a recombinant uricase, used in tumour lysis syndrome
Allopurinol interacts dangerously with azathioprine and 6-mercaptopurine, since xanthine oxidase normally degrades them; the dose must be cut substantially.