Roles of the enzyme xanthine oxidase and its products.
Purines and Pyrimidines Breakdown

Author: Elena Mosso
Date: 13/01/2012


The Enzyme.

Xanthine oxydase in also called xanthine oxidoreductase. It is an enzyme which is principally involved in purine catabolism : Kegg diagram, but also in caffeine metabolism: Kegg diagram, and some xenobiothics catabolism: Kegg diagram; xanthine oxidase is involved in xenobiothics catabolism, for example, it converts a pro drug (mercaptopurine) into the active form 6-Thioinosine-5’triphosphate. Mercaptopurine is employed as an immunosuppressor in therapies against autoimmune diseases or some forms of cancer.
Xanthine oxidase is an iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. It is distributed widely in various organs, especially in the gut and in the liver, but also in lungs, kidneys, heart, brain, plasma. The gene encoding this enzyme is localized on the short arm of chromosome 2. The enzyme oxidizes hypoxanthine to xanthine, and xanthine to uric acid, producing hydrogen peroxide. Reactions which involve the enzyme
Xanthine oxydase is involved in gout pathogenesis: the accumulation of uric acid cause its precipitation in kidneys and joints (in particular in metatarso-phalangeal joints). Uric acid, in fact, forms crystals which accumulates. To solve this problem, some drugs are used. They are called xanthine oxydase inhibitors:
* allopurinol is a non-selective xanthine oxidase inhibitor. It is a purinic analogue. The molecule
* febuxostat is a selective xanthine oxidase inhibitor. Febuxostat: a new treatment for Hyperuricaemia in gout, 2008

Metabolic Pathways.

Xanthine oxidase syntethizes uric acid and hydrogen peroxide. In gouty people, uric acid can accumulate and precipitate, leading to serious health problems. But uric acid is a molecule characterized not only by negative effects, but also it has an important role as an antioxidant, specially at low concentrations.

Uric Acid as an antioxidant

Uric Acid has an important role as an antioxidant, in fact in is an important peroxynitrite scavenger which protects the blood brain barrier from alterations of permeability. Moreover, it probably inhibits CNS inflammation. For this reason, it can be a protective factor against important diseases such as Multiple Sclerosis and Parkinson Disease. In fact, there is a huge evidence that PD patients have decreased levels of antioxidant enzyme activity and increased oxidative stress biomarkers. Urate has been demonstrated to reduce oxidation because it is a powerful scavengers of peroxyl radicals and hydroxyl radicals, and is able to inhibit free radical-initiated DNA damage; it can be oxidized by ROS and hemoprotein/H2O2 systems, converting them to inactive forms; moreover, it can complex with metal ions.
On the other hand, uric acid can not be considerated a prognostic or diagnostic biomarker fo Parkinson Disease because it is not specific for this disease. Moreover, today it can not be used as a treatment because it carries substantial health risks such as gout, urolithiasis and possible cardiovascular diseases.
Uric Acid and Oxydative Stress, 2005
Serum Uric Acid and Multiple Sclerosis , 2006(05)00146-0/abstract
Role of Uric Acid in Multiple Sclerosis, 2008
Uric acid and multiple sclerosis, 2004
Uric Acid, a Peroxynitrite Scavenger, Inhibits CNS Inflammation, Blood–CNS Barrier Permeability Changes, and Tissue Damage in a Mouse Model of Multiple Sclerosis , 2000
Urate: a Novel Biomarker of Parkinson’s Disease, 2011
Plasma Urate and Risk of Parkinson’s Disease, 2007

Other roles of xanthine oxidase.

Xanthine oxidase is an enzyme involved in several pathways. Some recent studies had noticed that xanthine oxydase espression is augmented in milk and lower in colostrums; this fact can be involved in the transition from colostrum to milk production. Moreover, the enzyme can probably be involved in regulation of adipogenesis, in particular the regulation of PPARγ activity.
Role in adipogenesis: Xanthine Oxidoreductase is a Regulator of Adipogenesis and PPARγ Activity, 2007
Role in the synthesis of colostrums and milk : Developmental changes in the milk fat globule membrane proteome during the transition from colostrum to milk, 2008(08)71181-0/abstract

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