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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Xanthine oxidase

Performs the last two steps of purine breakdown and makes uric acid; it is the target of allopurinol and febuxostat.

Updated 2026-11-01

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## Key facts

- Hypoxanthine → xanthine → uric acid, using O₂ (oxidase form) or NAD⁺ (dehydrogenase form).
- Cofactors: molybdenum (molybdopterin), FAD and two iron–sulfur clusters.
- Allopurinol: a hypoxanthine analogue; its metabolite oxypurinol stays bound to the molybdenum. Febuxostat: not a purine; it plugs the substrate channel.
- It also inactivates 6-mercaptopurine: with allopurinol, azathioprine and 6-MP accumulate and become toxic.

**Also called**
Xanthine oxidoreductase (xanthine dehydrogenase)

**EC number**
[1.17.3.2](https://www.enzyme-database.org/query.php?ec=1.17.3.2)

**Genes**
XDH

**Structure (PDB)**
[1N5X](https://www.rcsb.org/structure/1N5X)

## Regulation

- The dehydrogenase form converts to the oxidase by cysteine oxidation or proteolysis (ischaemia).
- The oxidase form produces superoxide and H₂O₂, contributing to reperfusion injury.

## Inhibitors and toxins

- Allopurinol (oxypurinol)
- Febuxostat
- Topiroxostat

## Clinical notes

- Xanthine oxidase inhibitors are the mainstay for lowering urate in chronic gout and preventing urate nephropathy.
- On allopurinol, hypoxanthine and xanthine accumulate; in Lesch-Nyhan syndrome they can form xanthine stones.
- Its inherited deficiency is xanthinuria: almost undetectable uric acid and xanthine stones.
- Carriers of the HLA-B*58:01 allele have a higher risk of severe skin reactions to allopurinol.

## Drugs that act here

- [Allopurinol](https://durgical.com/en/pharmacology/allopurinol/)
- [Febuxostat](https://durgical.com/en/pharmacology/febuxostat/)

## Pathways

- [Purine degradation and salvage](https://durgical.com/en/biochemistry/pathways/purine-degradation-and-salvage/)

## Related conditions

- [Gout](https://durgical.com/en/conditions/gout/)
- [Hereditary xanthinuria](https://durgical.com/en/conditions/hereditary-xanthinuria/)
- [Tumour lysis syndrome](https://durgical.com/en/conditions/tumour-lysis-syndrome/)
- [Kidney stones (urolithiasis)](https://durgical.com/en/conditions/kidney-stones/)

## Related

- [Uric acid](https://durgical.com/en/biochemistry/molecules/uric-acid/)
- [Hypoxanthine](https://durgical.com/en/biochemistry/molecules/hypoxanthine/)
- [Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)](https://durgical.com/en/biochemistry/enzymes/hypoxanthine-guanine-phosphoribosyltransferase/)
- [Adenine phosphoribosyltransferase (APRT)](https://durgical.com/en/biochemistry/enzymes/adenine-phosphoribosyltransferase/)
- [Drugs acting on nucleotide metabolism](https://durgical.com/en/biochemistry/topics/drugs-acting-on-nucleotide-metabolism/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which metal sits in the active site of xanthine oxidase?

Molybdenum, bound to molybdopterin; it also has FAD and iron–sulfur clusters.

## Why is combining allopurinol and azathioprine avoided without adjustment?

Xanthine oxidase inactivates 6-mercaptopurine; blocking it lets the drug build up and can cause severe myelosuppression.

## How do allopurinol and febuxostat differ?

Allopurinol is a purine analogue (oxypurinol binds the molybdenum); febuxostat is not a purine and blocks the substrate channel.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [XDH: Xanthine dehydrogenase/oxidase (human)](https://www.uniprot.org/uniprotkb/P47989/entry) (UniProt, 2026); [XDH gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/xdh/) (MedlinePlus, US National Library of Medicine, 2026); [1N5X: Xanthine Dehydrogenase from Bovine Milk with Inhibitor TEI-6720 Bound](https://www.rcsb.org/structure/1N5X) (RCSB Protein Data Bank, 2026); [Allopurinol: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682673.html) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/biochemistry/enzymes/xanthine-oxidase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/xanthine-oxidase/