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Xanthine oxidase

 

 
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Xanthine oxidase
 
 
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The enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 xanthine oxidase, or XO, catalyzes the oxidation of hypoxanthine
Hypoxanthine

Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine....
 to xanthine
Xanthine

Xanthine , , is a purine base found in most body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
 and can further catalyze the oxidation of xanthine to uric acid
Uric acid

Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3....
. This enzyme plays an important role in the catabolism of purines in some species, including humans.

Xanthine oxidase can be converted to xanthine dehydrogenase
Xanthine dehydrogenase

Xanthine dehydrogenase, also known as XDH, is a protein which in humans is encoded by the XDH gene....
 by reversible sulfhydryl oxidation.

following chemical reactions are catalyzed by xanthine oxidase:

protein is large, having a molecular weight of 270,000, and has 2 flavin
Flavin

Flavin is the common name for a group of organic compounds based on pteridine, formed by the Heterocycle isoalloxazine. The biochemical source is the vitamin riboflavin....
 molecules (bound as FAD), 2 molybdenum
Molybdenum

Molybdenum , is a Group 6 element chemical element with the symbol Mo and atomic number 42. It has the List of elements by melting point melting point of any element....
 atoms, and 8 iron
Iron

Iron is a chemical element with the symbol Fe and atomic number 26. Iron is a Group 8 element and period 4 element. Iron is lustrous and silvery in color....
 atoms bound per enzymatic unit.






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Encyclopedia


The enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 xanthine oxidase, or XO, catalyzes the oxidation of hypoxanthine
Hypoxanthine

Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids where it is present in the anticodon of tRNA in the form of its nucleoside inosine....
 to xanthine
Xanthine

Xanthine , , is a purine base found in most body tissues and fluids and in other organisms. A number of mild stimulants are derived from xanthine, including caffeine and theobromine....
 and can further catalyze the oxidation of xanthine to uric acid
Uric acid

Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3....
. This enzyme plays an important role in the catabolism of purines in some species, including humans.

Xanthine oxidase can be converted to xanthine dehydrogenase
Xanthine dehydrogenase

Xanthine dehydrogenase, also known as XDH, is a protein which in humans is encoded by the XDH gene....
 by reversible sulfhydryl oxidation.

Reaction

The following chemical reactions are catalyzed by xanthine oxidase:
  • hypoxanthine + H2O + O2 xanthine + H2O2
  • xanthine + H2O + O2 uric acid + H2O2


Protein structure

The protein is large, having a molecular weight of 270,000, and has 2 flavin
Flavin

Flavin is the common name for a group of organic compounds based on pteridine, formed by the Heterocycle isoalloxazine. The biochemical source is the vitamin riboflavin....
 molecules (bound as FAD), 2 molybdenum
Molybdenum

Molybdenum , is a Group 6 element chemical element with the symbol Mo and atomic number 42. It has the List of elements by melting point melting point of any element....
 atoms, and 8 iron
Iron

Iron is a chemical element with the symbol Fe and atomic number 26. Iron is a Group 8 element and period 4 element. Iron is lustrous and silvery in color....
 atoms bound per enzymatic unit. The molybdenum atoms are contained as molybdopterin
Molybdopterin

Molybdopterins are a class of cofactor found in most molybdenum and all tungsten enzymes. It consists of a pyranopterin, a complex heterocycle featuring a pyran fused to a pterin ring....
 cofactors and are the active sites of the enzyme. The iron atoms are part of [2Fe-2S] ferredoxin
Ferredoxin

Ferredoxins are iron-sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C....
 iron-sulfur cluster
Iron-sulfur cluster

For biological Fe-S clusters, see iron-sulfur proteins.Iron-sulfur clusters are ensembles of iron and sulfide centres. Fe-S clusters are most often discussed in the context of the biological role for iron-sulfur proteins....
s and participate in electron transfer reactions.

Catalytic mechanism

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

Oxo or OXO can refer to:...
), sulfur atoms and a terminal hydroxide
Hydroxide

In chemistry, hydroxide is the name for the Diatomic molecule anion OH-, consisting of oxygen and hydrogen atoms, usually derived from the Dissociation of a base ....
. In the reaction with xanthine to form uric acid, an oxygen atom is transferred from molybdenum to xanthine. The reformation of the active molybdenum center occurs by the addition of water. Like other known molybdenum-containing oxidoreductases, the oxygen atom introduced to the substrate
Substrate (biochemistry)

In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalysis chemical reactions involving the substrate. The substrate binds with the enzyme active site, and an enzyme-substrate complex is formed....
 by XO originates from water rather than from dioxygen (O2).

Clinical significance

In humans, xanthine oxidase is normally found in the liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 and not free in the blood. During severe liver damage, xanthine oxidase is released into the blood, so a blood assay for XO is a way to determine if liver
Liver

The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, a few of which are detoxification, protein synthesis, and production of biochemicals necessary for digestion....
 damage has happened.

As well, because xanthine oxidase is a metabolic pathway
Metabolic pathway

In biochemistry, a metabolic pathway is a series of chemistry reactions occurring within a cell . In each pathway, a principal chemical is modified by chemical reactions....
 for uric acid
Uric acid

Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3....
 formation, the xanthine oxidase inhibitor allopurinol
Allopurinol

Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout....
 is used in the treatment of gout
Gout

Gout is a crystal deposition disease hallmarked by elevated levels of uric acid in the Circulatory system. In this condition, crystals of monosodium urate or uric acid are deposited on the articular cartilage of joints, tendons and surrounding tissues....
.

Xanthinuria
Xanthinuria

Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the enzyme xanthine oxidase....
 is a rare genetic disorder
Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due in part to a genetic disorders, they can also be caused by Environment factors....
 where the lack of xanthine oxidase leads to high concentration of xanthine in blood and can cause health problems such as renal failure
Renal failure

Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. It is divided in acute and chronic forms; either form may be due to a large number of other medical problems....
. There is no specific treatment, sufferers are advised by doctors to avoid foods high in purine
Purine

Purine is a heterocyclic compound aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
 and to maintain a high fluid intake.

Inhibition of xanthine oxidase has been proposed as a mechanism for improving cardiovascular health.

Inhibitors

Inhibitors of XO include allopurinol
Allopurinol

Allopurinol is a drug used primarily to treat hyperuricemia and its complications, including chronic gout....
, oxypurinol
Oxypurinol

Oxypurinol is an inhibitor of xanthine oxidase.References...
, and phytic acid
Phytic acid

Phytic acid is the principal storage form of phosphorus in many plant Biological tissues, especially bran and seeds.Inositol penta- , tetra- , and triphosphate are also called phytates....
.

See also

  • xanthine dehydrogenase
    Xanthine dehydrogenase

    Xanthine dehydrogenase, also known as XDH, is a protein which in humans is encoded by the XDH gene....


  • sodium molybdate
    Sodium molybdate

    Sodium molybdate, Na2MoO4, is useful as a source of molybdenum. It is often found as the dihydrate, Na2MoO4?2H2O....


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