Xanthine (3,7-dihydro-purine-2,6-dione), is a
purineA purine is a heterocyclic 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....
baseFor the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
found in most human body tissues and fluids and in other organisms. A number of
stimulantStimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s are derived from xanthine, including
caffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
and
theobromineTheobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...
.
Xanthine is a product on the pathway of purine degradation.
- It is created from guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
by guanine deaminaseGuanine deaminase is an enzyme which converts guanine to xanthine.-External links:...
.
- It is created from 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. It has a tautomer known as 6-Hydroxypurine. Hypoxanthine is a necessary additive in certain cell,...
by xanthine oxidoreductase.
- It is also created from xanthosine
Xanthosine is a nucleoside derived from xanthine and ribose.-See also:* Xanthosine monophosphate* Xanthosine diphosphate* Xanthosine triphosphate...
by purine nucleoside phosphorylasePurine nucleoside phosphorylase also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by the NP gene.- Function :Purine nucleoside phosphorylase is an enzyme involved in purine metabolism...
(PNP).
Xanthine is subsequently converted to
uric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
by the action of the
xanthine oxidaseXanthine oxidase Xanthine oxidase Xanthine oxidase (XO (sometimes 'XAO'), a form of xanthine oxidoreductase that generates reactive oxygen species. Is an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and can further catalyze the oxidation of xanthine to uric acid...
enzyme.
Studies reported in 2008, based on
12C/
13C isotopic ratios of organic compounds found in the
Murchison meteoriteThe Murchison meteorite is named after Murchison, Victoria, in Australia. It is one of the most studied meteorites due to its large mass , the fact that it was an observed fall, and it belongs to a group of meteorites rich in organic compounds....
, suggested that xanthine and related chemicals, including the
RNARibonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
component
uracilUracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
, were formed extraterrestrially. In August 2011, a report, based on
NASAThe National Aeronautics and Space Administration is the agency of the United States government that is responsible for the nation's civilian space program and for aeronautics and aerospace research...
studies with meteorites found on
EarthEarth is the third planet from the Sun, and the densest and fifth-largest of the eight planets in the Solar System. It is also the largest of the Solar System's four terrestrial planets...
, was published suggesting xanthine and related organic molecules, including the
DNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and
RNARibonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
components
adenineAdenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...
and
guanineGuanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...
, were made in
outer spaceOuter space is the void that exists between celestial bodies, including the Earth. It is not completely empty, but consists of a hard vacuum containing a low density of particles: predominantly a plasma of hydrogen and helium, as well as electromagnetic radiation, magnetic fields, and neutrinos....
.
Pathology
People with the rare
genetic disorderA genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
xanthinuriaXanthinuria, 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.It was first formally characterized in 1954.-Causes:...
lack sufficient xanthine oxidase and cannot convert xanthine to
uric acidUric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
.
Clinical significance of xanthine derivatives
Derivatives of xanthine, known collectively as
xanthines, are a group of
alkaloidAlkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
s commonly used for their effects as mild
stimulantStimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s and as
bronchodilatorA bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing resistance in the respiratory airway and increasing airflow to the lungs. Bronchodilators may be endogenous , or they may be medications administered for the treatment of breathing difficulties...
s, notably in treating the symptoms of
asthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
. In contrast to other, more potent stimulants, their main effect consists mainly of opposing the actions of the sleepiness-inducing
adenosine, making them somewhat less effective as stimulants than
sympathomimetic amineSympathomimetic drugs mimic the effects of transmitter substances of the sympathetic nervous system such as catecholamines, epinephrine , norepinephrine , dopamine, etc...
s. Due to widespread effects, the therapeutic range of xanthines is narrow, making them merely a second-line asthma treatment. The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia.
Methylxanthines affect not only the airways but stimulate heart rate, force of contraction, cardiac arrhythmias at high concentrations. In the CNS they increase alertness, stimulate the respiratory centre, and are used for treatment of infantile apnea. In high doses they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce acid and pepsin secretions in the GI tract.
Methylxanthines are metabolized by Cytochrome P450 in the liver.
MethylatedIn the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
xanthines include
caffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
,
aminophyllineAminophylline is a bronchodilator. It is a compound of the bronchodilator theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves solubility, and the aminophylline is usually found as a dihydrate-Properties:...
,
IBMXIBMX, 3-isobutyl-1-methylxanthine, like other methylated xanthine derivatives, is both a# competitive nonselective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNF-alpha and leukotriene synthesis, and reduces inflammation and innate immunity and#...
,
paraxanthineParaxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine, structurally related to caffeine. Like caffeine, paraxanthine is a psychoactive central nervous system stimulant...
,
pentoxifylline,
theobromineTheobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...
, and
theophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
. These drugs act as both
- competitive nonselective phosphodiesterase inhibitors which raise intracellular cAMP
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
, activate PKAIn cell biology, Protein kinase A refers to a family of enzymes whose activity is dependent on cellular levels of cyclic AMP . PKA is also known as cAMP-dependent protein kinase...
, inhibit TNF-alphaTumor necrosis factor promotes the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, hidradenitis suppurativa and refractory asthma. These disorders are...
and leukotrieneLeukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
synthesis, and reduce inflammationAnti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
and innate immunity and
- nonselective adenosine receptor
The adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
antagonists which inhibit sleepiness-inducing adenosine.
But different analogues show varying potency at the numerous subtypes, and a wide range of synthetic xanthines (some nonmethylated) have been developed searching for compounds with greater selectivity for
phosphodiesterase enzymeA phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
or
adenosine receptorThe adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
subtypes. Xanthines are also found very rarely as constituents of
nucleic acidNucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
s.
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Selected Xanthines
| Name | R1 | R2 | R3 | IUPAC nomenclature A chemical nomenclature is a set of rules to generate systematic names for chemical compounds. The nomenclature used most frequently worldwide is the one created and developed by the International Union of Pure and Applied Chemistry ....
| Found In |
CaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
|
CH3 |
CH3 |
CH3 |
1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione |
CoffeeCoffee is a brewed beverage with a dark,init brooo acidic flavor prepared from the roasted seeds of the coffee plant, colloquially called coffee beans. The beans are found in coffee cherries, which grow on trees cultivated in over 70 countries, primarily in equatorial Latin America, Southeast Asia,...
, GuaranaGuarana , Paullinia cupana, syn. P. crysan, P. sorbilis) is a climbing plant in the maple family, Sapindaceae, native to the Amazon basin and especially common in Brazil. Guarana features large leaves and clusters of flowers, and is best known for its fruit, which is about the size of a coffee bean...
, Yerba mateMaté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...
, TeaTea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...
, KolaKola can refer to:*Kola nut, a genus of about 125 species of trees**Inca Kola, a cola soft drink made in Peru**Kola Real, a Peruvian soft drink**Kola Inglesa , a Peruvian soft drink...
|
TheobromineTheobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...
|
H |
CH3 |
CH3 |
3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione |
ChocolateChocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
, Yerba mateMaté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...
|
TheophyllineTheophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
|
CH3 |
CH3 |
H |
1,3-dimethyl-7H-purine-2,6-dione |
Tea Tea is an aromatic beverage prepared by adding cured leaves of the Camellia sinensis plant to hot water. The term also refers to the plant itself. After water, tea is the most widely consumed beverage in the world...
, chocolateChocolate is a raw or processed food produced from the seed of the tropical Theobroma cacao tree. Cacao has been cultivated for at least three millennia in Mexico, Central and South America. Its earliest documented use is around 1100 BC...
, Yerba mateMaté, yerba maté or erva maté , Ilex paraguariensis, is a species of holly native to subtropical South America in northeastern Argentina, Bolivia, southern Brazil, Uruguay and Paraguay...
|
| Xanthine |
H |
H |
H |
3,7-dihydro-purine-2,6-dione |
plants, animals |