Alloxan, sometimes referred to as ''alloxan hydrate'', is the name of the

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the formula OC(N(H)CO)₂C(OH)₂. It is classified as a derivative of

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...

. The

anhydrous A substance is anhydrous if it contains no water. Many processes in chemistry can be impeded by the presence of water; therefore, it is important that water-free reagents and techniques are used. In practice, however, it is very difficult to achie ...

derivative OC(N(H)CO)₂CO is also known, as well as a dimeric derivative. These are some of the earliest known organic compounds. They exhibit a variety of biological activities.

History and literature

The compound was discovered by Justus von Liebig and Friedrich Wöhler. It is one of the oldest named organic compounds. It was originally prepared in 1818 by

Luigi Valentino Brugnatelli Luigi Valentino Brugnatelli (also Luigi Gaspare Brugnatelli or Luigi Vincenzo Brugnatelli) (14 February 1761 in Pavia – 24 October 1818 in Pavia) was an Italian chemist and inventor who discovered the process for electroplating in 1805. Ear ...

(1761-1818) and was named in 1838 by Wöhler and

Liebig Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at the ...

. The name "Alloxan" emerged from an amalgamation of the words "

allantoin Allantoin is a chemical compound with formula C4H6N4O3. It is also called 5-ureidohydantoin or glyoxyldiureide. It is a diureide of glyoxylic acid. Allantoin is a major metabolic intermediate in most organisms including animals, plants and bacter ...

" and "Oxalsäure" (

oxalic acid Oxalic acid is an organic acid with the systematic name ethanedioic acid and formula . It is the simplest dicarboxylic acid. It is a white crystalline solid that forms a colorless solution in water. Its name comes from the fact that early inve ...

). The alloxan model of diabetes was first described in rabbits by Dunn, Sheehan and McLetchie in 1943. The name is derived from

, a product of

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 a product of the metabolic breakdown of ...

excreted by the

fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...

into the

allantois The allantois (plural ''allantoides'' or ''allantoises'') is a hollow sac-like structure filled with clear fluid that forms part of a developing amniote's conceptus (which consists of all embryonic and extraembryonic tissues). It helps the embryo ...

, and oxaluric acid derived from

and

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...

, found in

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

. Alloxan was used in the production of the purple dye

murexide Murexide (NH4C8H4N5O6, or C8H5N5O6·NH3), also called ammonium purpurate or MX, is the ammonium salt of purpuric acid. It is a purple solid that is soluble in water. The compound was once used as an indicator reagent. Aqueous solutions are yel ...

, discovered by

Carl Wilhelm Scheele Carl Wilhelm Scheele (, ; 9 December 1742 – 21 May 1786) was a Swedish German pharmaceutical chemist. Scheele discovered oxygen (although Joseph Priestley published his findings first), and identified molybdenum, tungsten, barium, hydrog ...

in 1776. Murexide is the product of the complex ''in-situ'' multistep reaction of alloxantin and gaseous

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

. Murexide results from the condensation of the unisolated intermediate uramil with alloxan, liberated during the course of the reaction. : Scheele sourced

from human calculi (such as

kidney stone Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine s ...

s) and called the compound lithic acid.

William Prout William Prout FRS (; 15 January 1785 – 9 April 1850) was an English chemist, physician, and natural theologian. He is remembered today mainly for what is called Prout's hypothesis. Biography Prout was born in Horton, Gloucestershire in 1 ...

investigated the compound in 1818 and he used

boa constrictor The boa constrictor (scientific name also ''Boa constrictor''), also called the red-tailed boa, is a species of large, non-venomous, heavy-bodied snake that is frequently kept and bred in captivity. The boa constrictor is a member of the family B ...

excrement with up to 90% ammonium acid urate. In the chapter "Nitrogen" of his memoir ''The Periodic Table'',

Primo Levi Primo Michele Levi (; 31 July 1919 – 11 April 1987) was an Italian chemist, partisan, writer, and Jewish Holocaust survivor. He was the author of several books, collections of short stories, essays, poems and one novel. His best-known works ...

tells of his futile attempt to make alloxan for a cosmetics manufacturer who has read that it can cause permanent reddening of the lips. Levi considers the droppings of

pythons The Pythonidae, commonly known as pythons, are a family of nonvenomous snakes found in Africa, Asia, and Australia. Among its members are some of the largest snakes in the world. Ten genera and 42 species are currently recognized. Distribution ...

as a source for uric acid for making alloxan, but he is turned down by the director of the

Turin Turin ( , Piedmontese language, Piedmontese: ; it, Torino ) is a city and an important business and cultural centre in Northern Italy. It is the capital city of Piedmont and of the Metropolitan City of Turin, and was the first Italian capital ...

zoo because the zoo already has lucrative contracts with pharmaceutical companies, so he is obliged to use

chicken The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult m ...

s as his source of uric acid. The synthesis fails, however, "and the alloxan and its resonant name remained a resonant name."

Synthesis

It was originally obtained by oxidation of

nitric acid Nitric acid is the inorganic compound with the formula . It is a highly corrosive mineral acid. The compound is colorless, but older samples tend to be yellow cast due to decomposition into oxides of nitrogen. Most commercially available nitri ...

. It is prepared by oxidation of

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 ...

chromium trioxide Chromium trioxide (also known as chromium(VI) oxide or chromic anhydride) is an 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-purple ...

. A dimeric derivative alloxantin can be prepared by partial reduction of alloxan with hydrogen sulfide. :

Biological effects

Alloxan is a toxic

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

analogue, which selectively destroys

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

-producing cells in the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...

(that is,

beta cell Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimini ...

s) when administered to

rodent Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are na ...

s and many other animal species. This causes an insulin-dependent

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

(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 2 (GLUT2) also known as solute carrier family 2 (facilitated glucose transporter), member 2 (SLC2A2) is a transmembrane carrier protein that enables protein facilitated glucose movement across cell membranes. It is the principa ...

glucose transporter. Alloxan, in the presence of intracellular

thiol In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...

s, generates

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...

(ROS) in a cyclic reaction with its reduction product, dialuric acid. The beta cell toxic action of alloxan is initiated by

free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Ailments of unknown cause Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabo ...

s formed in this

redox reaction Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

. Studies 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.

Impact upon beta cells

Because it selectively kills the

-producing

beta-cells Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dimi ...

found in the pancreas, alloxan is used to induce

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

in laboratory animals. This occurs most likely because of selective uptake of the compound due to its structural similarity to

as well as the beta-cell's highly efficient uptake mechanism (GLUT2). In addition, alloxan has a high affinity to SH-containing cellular compounds and, as a result, reduces glutathione content. Furthermore, alloxan inhibits glucokinase, a SH-containing protein essential for insulin secretion induced by glucose. Most studies have shown that alloxan is not toxic to the human beta-cell, even in very high doses, probably because of differing glucose uptake mechanisms in humans and rodents. Alloxan is, however, toxic to the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

and the

kidneys The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

in high doses.

References

External links