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Information about Xanthine Oxidoreductase

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Xanthine Oxidase
The enzyme xanthine oxidase, or XO, (bovine milk enzyme is PDB 1FIQ, EC 1.17.3.2) catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid

Reaction

  • hypoxanthine + O2 + H2O ↔ xanthine + H2O2
  • xanthine + O2 + H2O ↔ uric acid + H2O2



hypoxanthine (One oxygen)

xanthine (Two oxygens)

uric acid (Three oxygens. Diagram is rotated.)


Protein structure

The protein is large, having a molecular weight of 270,000, and has 2 flavin molecules (bound as FAD), 2 molybdenum atoms, and 8 iron atoms bound per enzymatic unit. The molybdenum atoms are contained as molybdopterin cofactors and are the active sites of the enzyme. The iron atoms are part of [2Fe-2S] ferredoxin iron-sulfur clusters and participate in electron transfer reactions.

Active site and mechanism of xanthine oxidase

The active site of XO is composed of a molybdopterin unit with the molybdenum atom also coordinated by terminal oxygen (oxo), sulfur atoms and a terminal hydroxide. 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 by XO originates from water rather than from dioxygen (O2).

Xanthine oxidase and disease

In humans, xanthine oxidase is normally found in the liver 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 damage has happened. As well, because xanthine oxidase is a metabolic pathway for uric acid formation, the xanthine oxidase inhibitor allopurinol is used in the treatment of gout.

Xanthinuria is a rare genetic disorder where the lack of xanthine oxidase leads to high concentration of xanthine in blood and can cause health problems such as renal failure. There is no specific treatment, sufferers are advised by doctors to avoid foods high in purine and to maintain a high fluid intake.

See also

References

External links



 •  • [ e]
Other oxidoreductases (EC 1.15-1.18)
1.15 - Acting on superoxide as acceptorSuperoxide dismutase
1.16 - Oxidizing metal ionsCeruloplasmin
1.17 - Acting on CH or CH2 groupsXanthine oxidase - Ribonucleotide reductase
1.18 - Acting on iron-sulfur proteins as donorsNitrogenase
 •  • [ e]
Nucleotide metabolism enzymes
Purine metabolismsynthesis: Amidophosphoribosyltransferase - Inosine monophosphate synthase - GMP (IMP dehydrogenase, GMP synthase, GMP reductase) - AMP (Adenylosuccinate synthase, Adenylosuccinate lyase, AMP deaminase) - degradation: Purine nucleoside phosphorylase - Adenosine deaminase - Guanine deaminase - Xanthine oxidase - Urate oxidase
Nucleotide salvageHypoxanthine-guanine phosphoribosyltransferase - Adenine phosphoribosyltransferase
Pyrimidine metabolismCAD (Carbamoyl phosphate synthase II, Aspartate carbamoyltransferase, Dihydroorotase) - Dihydroorotate dehydrogenase - Orotidine 5'-phosphate decarboxylase - CTP synthase
DeoxyribonucleotideRibonucleotide reductase - Nucleoside-diphosphate kinase - DCMP deaminase - Thymidylate synthase
Enzymes are proteins that catalyze (i.e. accelerate) chemical reactions.[1] In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products.
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Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. This data, typically obtained by X-ray crystallography or NMR spectroscopy, is submitted by biologists and biochemists from around the world, is released into the public domain,
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Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. As a system of enzyme nomenclature, every EC number is associated with a recommended name for the respective enzyme.
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Redox (shorthand for reduction/oxidation reaction) describes all chemical reactions in which atoms have their oxidation number (oxidation state) changed.

This can be either a simple redox process such as the oxidation of carbon to yield carbon dioxide, or the
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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.
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Not to be confused with xanthene.


Xanthine (IPA: /ˈzænθiːn, ˈzænθaɪn]/
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Uric acid (or urate) is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3.

Metabolic processes

Xanthine oxidase oxidizes oxypurines such as xanthine and hypoxanthine to uric acid.
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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.
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Not to be confused with xanthene.


Xanthine (IPA: /ˈzænθiːn, ˈzænθaɪn]/
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Uric acid (or urate) is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3.

Metabolic processes

Xanthine oxidase oxidizes oxypurines such as xanthine and hypoxanthine to uric acid.
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molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12).
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Flavin is a tricyclic heteronuclear organic ring based on pteridine whose biochemical source is the vitamin riboflavin. The flavin moiety is often attached with an adenosine diphosphate to form flavin adenine dinucleotide (FAD
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6
(strongly acidic oxide)
Electronegativity 2.16 (scale Pauling)
Ionization energies
(more) 1st: 684.3 kJmol−1
2nd: 1560 kJmol−1
3rd: 2618 kJmol−1
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3, 4, 6
(amphoteric oxide)
Electronegativity 1.83 (Pauling scale)
Ionization energies
(more) 1st: 762.5 kJmol−1
2nd: 1561.9 kJmol−1
3rd: 2957 kJmol−1

Atomic radius 140 pm
Atomic radius (calc.
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Molybdopterins are a class of biochemical cofactors that are used in many different enzymes. The simplest structure of molybdopterin contains a pyranopterin coordinated to molybdenum. The pyranopterin structure is a fused ring system containing a pyran fused to pterin.
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Ferredoxins (from Latin ferrum: iron + redox, often abbreviated "fd") are iron-sulfur proteins that mediate electron transfer in a range of metabolic reactions.

Overview

The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co.
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An iron-sulfur cluster is a structural motif found in a variety of metalloproteins, such as the ferredoxins, as well as NADH dehydrogenase and Coenzyme Q - cytochrome c reductase, and nitrogenase.
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Oxo or OXO can refer to:
  • In chemistry:
  • oxo, the formal IUPAC nomenclature for a ketone functional group. However, other prefixes are also used by various books and journals.

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In chemistry, hydroxide is the most common name for the diatomic anion OH−, consisting of oxygen and hydrogen atoms, usually derived from the dissociation of a base. It is one of the simplest diatomic ions known.
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In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate(s). The substrate binds with the enzyme's active site, and an enzyme-substrate complex is formed.
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2, −1
(neutral oxide)
Electronegativity 3.44 (Pauling scale)
Ionization energies
(more) 1st: 1313.9 kJmol−1
2nd: 3388.3 kJmol−1
3rd: 5300.5 kJmol−1

Atomic radius 60 pm
Atomic radius (calc.
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liver is an organ present in vertebrates and some other animals. It plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, and detoxification.
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liver is an organ present in vertebrates and some other animals. It plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, and detoxification.
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In biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. In each pathway a principal chemical is modified by chemical reactions. These reactions are accelerated, more accurately catalyzed, by enzymes.
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Uric acid (or urate) is an organic compound of carbon, nitrogen, oxygen and hydrogen with the formula C5H4N4O3.

Metabolic processes

Xanthine oxidase oxidizes oxypurines such as xanthine and hypoxanthine to uric acid.
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Allopurinol is a drug used primarily to treat conditions arising from excess uric acid, most notably chronic gout. Allopurinol does not alleviate acute attacks of gout, but is useful in preventing recurrence. Allopurinol has been used in the United States since 1964.
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Gout
Classification & external resources

Uric acid
ICD-10 M 10.
ICD-9 274.0 274.1 274.8 274.9

OMIM 138900 300323
DiseasesDB 29031

eMedicine med/924   orthoped/124 emerg/221 med/1112 oph/506 radio/313
MeSH D006073 Gout
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Xanthinuria
Classification & external resources

The structure of xanthine.
ICD-10 E 79.8
ICD-9 277.2

OMIM 278300 603592
DiseasesDB 14194 29821

eMedicine ped/2452   Xanthinuria, also known as Xanthine oxydase deficiency
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A genetic disorder is a condition caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due to genetic abnormalities acquired in a few cells during life, the term "genetic disease" most commonly refers to diseases present in all cells of the body
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MeSH C12.777.419.780.500 Renal failure or kidney failure is the condition in which the kidneys fail to function adequately.

Biochemically, it is typically detected by an elevated serum creatinine.
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