Urea

Overview
Urea is an organic compound with the chemical formula (NH2)2CO.

Urea is also known as carbamide, especially in the recommended International Nonproprietary Names (rINN) in use in Europe. For example, the medicinal compound hydroxyurea (old British Approved Name) is now hydroxycarbamide. Other names include carbamide resin, isourea, carbonyl diamide, and carbonyldiamine.

It was the first organic compound to be artificially synthesized from inorganic starting materials, thus dispelling the concept of vitalism.

Discovery
Urea was discovered by Hilaire Rouelle in 1773. It was the first organic compound to be artificially synthesized from inorganic starting materials, in 1828 by Friedrich Wöhler, who prepared it by the reaction of potassium cyanate with ammonium sulfate. Although Woehler was attempting to prepare ammonium cyanate, by forming urea, he inadvertently disproved vitalism, the theory that the chemicals of living organisms are fundamentally different from inanimate matter, thus starting the discipline of organic chemistry.

This discovery prompted Wohler to write triumphantly to Berzelius:

"I must tell you that I can make urea without the use of kidneys, either man or dog. Ammonium cyanate is urea."

It is found in mammalian and amphibian urine as well as in some fish. Birds and reptiles excrete uric acid, comprising a different form of nitrogen metabolism that requires less water.

Structure
Urea is highly soluble in water and is therefore an efficient way for the human body to expel excess nitrogen. Due to extensive hydrogen bonding with water (up to six hydrogen bonds may form, two from oxygen atom and one from each hydrogen), it is very soluble and thus is also a good fertilizer.

The urea molecule is planar and retains its full molecular point symmetry. Each carbonyl oxygen atom accepts four N-H-O hydrogen bonds, a very unusual feature for such a bond type. This dense (and energetically quite favourable) hydrogen bond network is probably established at the cost of efficient molecular packing: the structure is quite open, the ribbons forming tunnels with square cross-section.

Physiology
The individual atoms that make up a urea molecule come from carbon dioxide, water, aspartate and ammonia in a metabolic pathway known as the urea cycle, an anabolic process. This expenditure of energy is necessary because ammonia, a common metabolic waste product, is toxic and must be neutralized. Urea production occurs in the liver and is under the regulatory control of N-acetylglutamate.

The urea cycle was originally known as the Krebs-Henseleit cycle after it was partially deduced by Hans Adolf Krebs and Kurt Henseleit in 1932. Its details were clarified in the 1940s as the roles of citrulline and argininosuccinate as intermediates were understood. In this cycle, amino groups donated by ammonia and L-aspartate are converted to urea, while L-ornithine, citrulline, L-argininosuccinate, and L-arginine act as intermediates.

Most organisms have to deal with the excretion of nitrogen waste originating from protein and amino acid catabolism. In aquatic organisms the most common form of nitrogen waste is ammonia, while land-dwelling organisms convert the toxic ammonia to either urea or uric acid. Generally, birds and saurian reptiles excrete uric acid, while the remaining species, including mammals, excrete urea. Remarkably, tadpoles excrete ammonia, and shift to urea production during metamorphosis. In veterinary medicine, Dalmatian breeds of dogs are noteworthy in that they excrete urea in the form of uric acid in the urine rather than in the urea form. This is due to a defect in one of the genes controlling expression of the conversion enzymes in the urea cycle.

Despite the generalization above, the pathway has been documented not only in mammals and amphibians, but in many other organisms as well, including birds, invertebrates, insects, plants, yeast, fungi, and even microorganisms.

Urea is essentially a waste product, but is vital for forming hypertonic (concentrated) urine. In the distal portions of the kidney collecting duct, urea is reintroduced into the kidney medulla to raise osmolarity. Afterwards, water flowing through the collecting tubule flows back into the body by osmosis through aquaporins.

Urea is dissolved in blood (in humans in a concentration of 2.5 - 7.5 mmol/liter) and excreted by the kidney in the urine.

In addition, a small amount of urea is excreted (along with sodium chloride and water) in human sweat.

Hazards
Urea can be irritating to skin and eyes. Too high concentrations in the blood can cause damage to organs of the body. Low concentrations of urea such as in urine are not dangerous.

It has been found that urea can cause algal blooms to produce toxins, and urea in runoff from fertilizers may play a role in the increase of toxic blooms.

Repeated or prolonged contact with urea in fertiliser form on the skin may cause dermatitis. The substance also irritates the eyes, the skin and the respiratory tract. The substance decomposes on heating above melting point producing toxic gases. Reacts violently with strong oxidants, nitrites, inorganic chlorides, chlorites and perchlorates causing fire and explosion hazard

Laboratory use
Urea is a powerful protein denaturant. This property can be exploited to increase the solubility of some proteins. For this application it is used in concentrations up to 10 M. Urea is used to effectively disrupt the noncovalent bonds in proteins. Urea is an ingredient in the synthesis of urea nitrate. Urea nitrate is also a high explosive very similar to ammonium nitrate, however it may even be more powerful because of its complexity. VOD is 11,000 fps to 15,420 fps.

Medical use
Urea is used in topical dermatological products to promote rehydration of the skin. If covered by an occlusive dressing, 40% urea preparations may also be used for nonsurgical debridement of nails.
 * Drug use

See blood urea nitrogen ("BUN") for a commonly performed urea test, and marker of renal function.
 * Clinical diagnosis

Isotopically-labeled urea (carbon 14 - radioactive, or carbon 13 - stable isotope) is used in the Urea breath test, which is used to detect the presence of Helicobacter pylori (H. pylori, a bacterium) in the stomach and duodenum of humans. The test detects the characteristic enzyme urease, produced by H. pylori, by a reaction that produces ammonia from urea. This increases the pH (reduces acidity) of the stomach environment around the bacteria.
 * Other diagnostic use

Similar bacteria species to H. pylori can be identified by the same test in animals (apes, dogs, cats - including big cats).

Ureas
Ureas or carbamides are a class of chemical compounds sharing the same functional group RR'N-CO-NRR' based on a carbonyl group flanked by two organic amine residues. They can be accessed in the laboratory by reaction of phosgene with primary or secondary amines. Example of ureas are the compounds carbamide peroxide, allantoin and Hydantoin. Ureas are closely related to biurets and structurally related to amides, carbamates, diimides, carbodiimides and thiocarbamides.

Reactions
Urea reacts with alcohols to form urethanes. Urea reacts with malonic esters to make barbituric acids.