Xanthine oxidase

Xanthine oxidase (XO, sometimes 'XAO') is a form of xanthine oxidoreductase, a type of

• hypoxanthine + H₂O + O₂ ⇌ xanthine + H₂O₂
• xanthine + H₂O + O₂ ⇌ uric acid + H₂O₂
• Xanthine oxidase can also act on certain other purines, pterins, and aldehydes. For example, it efficiently converts 1-methylxanthine (a metabolite of caffeine) to 1-methyluric acid, but has little activity on 3-methylxanthine.^[8]
• Under some circumstances it can produce superoxide ions: RH + H₂O + 2 O₂ ⇌ ROH + 2 O⁻
  ₂ + 2 H⁺.^[5]

• 
  hypoxanthine (one oxygen atom)
• 
  xanthine (two oxygens)
• 
  uric acid (three oxygens)

Other reactions

Because XO is a superoxide-producing enzyme, with general low specificity,^[9] it can be combined with other compounds and enzymes and create reactive oxidants, as well as oxidize other substrates.

Bovine xanthine oxidase (from milk) was originally thought to have a binding site to reduce cytochrome c with, but it has been found that the mechanism to reduce this protein is through XO's superoxide anion byproduct, with competitive inhibition by carbonic anhydrase.^[10]

Another reaction catalyzed by xanthine oxidase is the decomposition of S-nitrosothiols (RSNO), a class of reactive nitrogen species, to nitric oxide (NO), which reacts with a superoxide anion to form peroxynitrite under aerobic conditions.^[11]

XO has also been found to produce the strong one-electron oxidant carbonate radical anion from oxidation with acetaldehyde in the presence of catalase and bicarbonate. It was suggested that the carbonate radical was likely produced in one of the enzyme's redox centers with a peroxymonocarbonate intermediate.^[9]

Here is a diagram highlighting the pathways catalyzed by xanthine oxidase.

It is suggested that xanthine oxidoreductase, along with other enzymes, participates in the conversion of nitrate to nitrite in mammalian tissues.^[12]

Protein structure

The protein is large, having a

Catalytic mechanism

The active site of XO is composed of a molybdopterin unit with the molybdenum atom also coordinated by terminal oxygen (

Clinical significance

Xanthine oxidase is a superoxide-producing enzyme found normally in serum and the lungs, and its activity is increased during influenza A infection.^[13]

During severe liver damage, xanthine oxidase is released into the blood, so a blood assay for XO is a way to determine if liver damage has happened.^[14]

Because xanthine oxidase is a

Increased concentration of serum uric acid has been under research as an indicator for cardiovascular health factors, and has been used to strongly predict mortality, heart transplant, and more in patients.[16] But it is not clear whether this could be a direct or casual association or link between serum uric acid concentration (and by proxy, xanthine oxidase activity) and cardiovascular health.^[19] States of high cell turnover and alcohol ingestion are some of the most prominent cases of high serum uric acid concentrations.^[18]

Reactive nitrogen species, such as peroxynitrite that xanthine oxidase can form, have been found to react with DNA, proteins, and cells, causing cellular damage or even toxicity. Reactive nitrogen signaling, coupled with reactive oxygen species, have been found to be a central part of myocardial and vascular function, explaining why xanthine oxidase is being researched for links to cardiovascular health.^[20]

Both xanthine oxidase and xanthine oxidoreductase are also present in corneal epithelium and endothelium and may be involved in oxidative eye injury.^[21]

Inhibitors

Inhibitors of XO include

• Xanthine dehydrogenase
• Sodium molybdate

References