Alloxan
Encyclopedia
Alloxan is an oxygenated pyrimidine
derivative. It is present as alloxan hydrate
in aqueous solution.
" and "Oxalsäure" (oxalic acid
).
analogue, which selectively destroys insulin-producing cells in the pancreas (that is beta cells) when administered to rodents and many other animal species. This causes an insulin-dependent diabetes mellitus (called "Alloxan Diabetes") in these animals, with characteristics similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially accumulates in beta cells through uptake via the GLUT2 glucose transporter. Alloxan, in the presence of intracellular thiols, generates reactive oxygen species
(ROS) in a cyclic reaction with its reduction product, dialuric acid. The beta cell toxic action of alloxan is initiated by free radicals formed in this redox reaction. One study suggests that alloxan does not cause diabetes in humans. Others found a significant difference in alloxan plasma levels in children with and without diabetes Type 1.
and Friedrich Wöhler
following the discovery of urea
in 1828 and is one of the oldest named organic compounds that exist. The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan and McLetchie in 1943.
, a product of uric acid
excreted by the fetus
into the allantois
and oxaluric acid derived from oxalic acid
and urea
, found in urine
.
by nitric acid
. In another method the monohydrate is prepared by oxidation of barbituric acid
by chromium trioxide
Alloxan is a strong oxidizing agent
and it forms a hemiacetal
with its reduced reaction product dialuric acid (in which a carbonyl
group is reduced to a hydroxyl
group) which is called alloxantin.
. Carl Wilhelm Scheele
discovered the dye in 1776. Murexide is the product of the complex in-situ multistep reaction of alloxantin and gaseous ammonia
. Murexide results from the condensation of the unisolated intermediate uramil with alloxan, liberated during the course of the reaction.
Scheele sourced uric acid
from human calculi (such as kidney stone
s) and called the compound lithic
acid. William Prout
investigated the compound in 1818 and he used boa constrictor
excrement with up to 90% ammonium acid urate.
Liebig and Wöhler in the nineteenth century coined the name murexide for the dye after the Trunculus Murex which is the source of the Tyrian purple of antiquity.
Primo Levi
in his novel The Periodic Table in chapter Nitrogen considers pythons as a source for alloxane on behalf of a lipstick
producer but he is turned down by the director of the Turin
zoo because the zoo already has lucrative contracts with cosmetics companies.
-producing beta-cells found in the pancreas, alloxan is used to induce diabetes in laboratory animals. This occurs most likely because of selective uptake of the compound due to its structural similarity to glucose
as well as the beta-cell's highly efficient uptake mechanism (GLUT2
).
However, alloxan is not toxic to the human beta-cell, even in very high doses, probably due to differing glucose uptake mechanisms in humans and rodents.Alloxan is, however, toxic to the liver
and the kidneys in high doses.
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
derivative. It is present as alloxan hydrate
Hydrate
Hydrate is a term used in inorganic chemistry and organic chemistry to indicate that a substance contains water. The chemical state of the water varies widely between hydrates, some of which were so labeled before their chemical structure was understood....
in aqueous solution.
History
Alloxan was originally isolated in 1818 by Brugnatelli and was named in 1838 by Wöhler and Liebig. The name "Alloxan" emerged from an amalgamation of the words "AllantoinAllantoin
Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid....
" and "Oxalsäure" (oxalic acid
Oxalic acid
Oxalic acid is an organic compound with the formula H2C2O4. This colourless solid is a dicarboxylic acid. In terms of acid strength, it is about 3,000 times stronger than acetic acid. Oxalic acid is a reducing agent and its conjugate base, known as oxalate , is a chelating agent for metal cations...
).
Biological effects
Alloxan is a toxic glucoseGlucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
analogue, which selectively destroys insulin-producing cells in the pancreas (that is beta cells) when administered to rodents and many other animal species. This causes an insulin-dependent diabetes mellitus (called "Alloxan Diabetes") in these animals, with characteristics similar to type 1 diabetes in humans. Alloxan is selectively toxic to insulin-producing pancreatic beta cells because it preferentially accumulates in beta cells through uptake via the GLUT2 glucose transporter. Alloxan, in the presence of intracellular thiols, generates reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
(ROS) in a cyclic reaction with its reduction product, dialuric acid. The beta cell toxic action of alloxan is initiated by free radicals formed in this redox reaction. One study suggests that alloxan does not cause diabetes in humans. Others found a significant difference in alloxan plasma levels in children with and without diabetes Type 1.
Discovery
The compound was discovered by Justus von LiebigJustus von Liebig
Justus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
and Friedrich Wöhler
Friedrich Wöhler
Friedrich Wöhler was a German chemist, best known for his synthesis of urea, but also the first to isolate several chemical elements.-Biography:He was born in Eschersheim, which belonged to aau...
following the discovery of urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
in 1828 and is one of the oldest named organic compounds that exist. The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan and McLetchie in 1943.
Etymology
The name is derived from allantoinAllantoin
Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid....
, a product of uric acid
Uric acid
Uric 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...
excreted by the fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
into the allantois
Allantois
Allantois is a part of a developing animal conceptus . It helps the embryo exchange gases and handle liquid waste....
and oxaluric acid derived from oxalic acid
Oxalic acid
Oxalic acid is an organic compound with the formula H2C2O4. This colourless solid is a dicarboxylic acid. In terms of acid strength, it is about 3,000 times stronger than acetic acid. Oxalic acid is a reducing agent and its conjugate base, known as oxalate , is a chelating agent for metal cations...
and urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
, found in urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
.
Synthesis
The original preparation for alloxan was by oxidation of uric acidUric acid
Uric 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 nitric acid
Nitric acid
Nitric acid , also known as aqua fortis and spirit of nitre, is a highly corrosive and toxic strong acid.Colorless when pure, older samples tend to acquire a yellow cast due to the accumulation of oxides of nitrogen. If the solution contains more than 86% nitric acid, it is referred to as fuming...
. In another method the monohydrate is prepared by oxidation of barbituric acid
Barbituric acid
Barbituric acid or malonylurea or 6-hydroxyuracil is an organic compound based on a pyrimidine heterocyclic skeleton. It is an odorless powder soluble in water. Barbituric acid is the parent compound of barbiturate drugs, although barbituric acid itself is not pharmacologically active...
by chromium trioxide
Chromium trioxide
Chromium trioxide is the inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name.This compound is a dark-red/orange brown solid, which dissolves in water concomitant with hydrolysis...
Alloxan is a strong oxidizing agent
Oxidizing agent
An oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...
and it forms a hemiacetal
Hemiacetal
Hemiacetals and hemiketals are compounds that are derived from aldehydes and ketones respectively. The Greek word hèmi means half...
with its reduced reaction product dialuric acid (in which a carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
group is reduced to a hydroxyl
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
group) which is called alloxantin.
Commercial use
Alloxane is a raw material for the production of the purple dye murexideMurexide
Murexide , also called ammonium purpurate or MX, is the ammonium salt of purpuric acid. It may be prepared by heating alloxantin in ammonia gas to 100 °C, or by boiling uramil with mercury oxide. W.N...
. Carl Wilhelm Scheele
Carl Wilhelm Scheele
Carl Wilhelm Scheele was a German-Swedish pharmaceutical chemist. Isaac Asimov called him "hard-luck Scheele" because he made a number of chemical discoveries before others who are generally given the credit...
discovered the dye in 1776. Murexide is the product of the complex in-situ multistep reaction of alloxantin and gaseous ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
. Murexide results from the condensation of the unisolated intermediate uramil with alloxan, liberated during the course of the reaction.
Scheele sourced uric acid
Uric acid
Uric 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...
from human calculi (such as kidney stone
Kidney stone
A kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s) and called the compound lithic
Lithic
Lithic may refer to:*a stone tool*Lithic analysis*Lithic stage*Lithic core *Lithic reduction *Lithic technology *Lithic flake *Lithic fragment...
acid. William Prout
William Prout
William Prout FRS was an English chemist, physician, and natural theologian. He is remembered today mainly for what is called Prout's hypothesis.-Biography:...
investigated the compound in 1818 and he used boa constrictor
Boa (genus)
Boa is a genus of non-venomous boas found in Mexico, Central and South America, Madagascar and on Reunion Island. Four species are currently recognized.The largest member of this group, B...
excrement with up to 90% ammonium acid urate.
Liebig and Wöhler in the nineteenth century coined the name murexide for the dye after the Trunculus Murex which is the source of the Tyrian purple of antiquity.
Primo Levi
Primo Levi
Primo Michele Levi was an Italian Jewish chemist and writer. He was the author of two novels and several collections of short stories, essays, and poems, but is best known for If This Is a Man, his account of the year he spent as a prisoner in the Auschwitz concentration camp in Nazi-occupied Poland...
in his novel The Periodic Table in chapter Nitrogen considers pythons as a source for alloxane on behalf of a lipstick
Lipstick
Lipstick is a cosmetic product containing pigments, oils, waxes, and emollients that applies color, texture, and protection to the lips. Many varieties of lipstick are known. As with most other types of makeup, lipstick is typically, but not exclusively, worn by women...
producer but he is turned down by the director of the Turin
Turin
Turin is a city and major business and cultural centre in northern Italy, capital of the Piedmont region, located mainly on the left bank of the Po River and surrounded by the Alpine arch. The population of the city proper is 909,193 while the population of the urban area is estimated by Eurostat...
zoo because the zoo already has lucrative contracts with cosmetics companies.
Impact upon beta cells
Because it selectively kills the insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-producing beta-cells found in the pancreas, alloxan is used to induce diabetes in laboratory animals. This occurs most likely because of selective uptake of the compound due to its structural similarity to glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
as well as the beta-cell's highly efficient uptake mechanism (GLUT2
GLUT2
Glucose transporter 2 also known as solute carrier family 2 , member 2 is a transmembrane carrier protein that enables passive glucose movement across cell membranes. It is the principal transporter for transfer of glucose between liver and blood, and for renal glucose reabsorption...
).
However, alloxan is not toxic to the human beta-cell, even in very high doses, probably due to differing glucose uptake mechanisms in humans and rodents.Alloxan is, however, toxic to the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and the kidneys in high doses.