Urea (chemical compound)

Urea, also known as carbamide, is a nitrogenous compound that is formed in vivo in the liver through the deamination, or removal of an amine group, from amino acids during the formation of ammonia. It has a carbonyl group with two attached amine groups that is formed during osmotic diuretic activity, or the inhibition of reabsorbing water and sodium during urine excretion. It is primary product of protein catabolism and encompasses approximately half of the overall urinary solids in all mammals and certain fish species. Urea promotes water and blood flow through the tissues that is advantageous for brain functionality as well as the interstitial fluid and plasma in the eyes and spinal column. By elevating water and blood flow, pressure within the tissues decreases thus allowing constant outflow of urine. Urea is also produced using laboratory techniques to supply larger amounts of the compound for industrial uses. Its colorless, crystalline structure allows urea to be an important compound in the fertilizer and feed, plastics, and drug industries.

Background

In 1773, urea was first chemically separated from urine by French chemist Hilaire-Marin Rouelle. However, it was not until 1828 when the German chemist Friedrich Wöhler prepared urea from ammonium cyanate that the laboratory synthesis of a natural organic chemical compound was widely accepted from the isolation of inorganic materials. Urea is currently synthesized and prepared commercially from industrial-sized amounts of liquid ammonia and liquid carbon dioxide.

Urea is prepared from ammonia and carbon dioxide. Ammonia is produced through the Haber process, where nitrogen and hydrogen react in the presence of an iron catalyst. Ammonia and carbon dioxide are first fed into a high-pressure reactor to form urea in a two-step equilibrium reaction: ammonium carbamate (NH₂COONH₄) is first formed followed by a deamination step to produce urea and water. Urea includes unreacted ammonia, carbon dioxide, and ammonium carbamate. Reducing the pressure and supplying heat decays ammonium carbamate back to ammonia and carbon dioxide. In industrial settings, unreacted ammonia and carbon dioxide are recycled back to the reactor feed to minimize reactant waste and increase the overall production of ammonium carbamate and urea.

The manufacturing of urea reacts compressed ammonia and carbon dioxide to maximize the production of urea while restraining the undesirable formation of biuret (NH₂CONHCONH₂). The compressed reactants first form ammonium carbamate through an exothermic reaction that releases heat in a boiler to produce steam. Two consecutive reactors then produce urea, where the products of the first reactor separate and purify the liquid before leading the gas products to the second reactor. The second reactor produces urea and recycles any unreacted carbon dioxide and ammonia solution to the initial inlet stream of the process.

Urea purification separates the major impurities, primarily water, from the urea production reaction and unreacted ammonia, carbon dioxide, and ammonium carbamate, in three flash stages. Flash separation stages partially vaporize the product to allow distinct separation between the unwanted liquid solution and the desired gas product. A lower pressure is used while heating the urea, allowing the ammonium carbamate to decompose back into ammonia and carbon dioxide. Water is recycled back to the second reactor, while excess ammonia is purified and returned to the inlet stream of the first reactor. Laboratory production of urea analyzes the various stages of granulation to determine the appropriate size distribution, amending the final urea sizes according to the size specifications of the company and the consumer. The final product is evaluated based on its moisture, biuret composition, formaldehyde composition, and pH.

Overview

The urea cycle for mammals is an essential metabolic process that converts toxic ammonia into urea by carrier molecules and enzymes within the liver. It is essential for the body to remove the nitrogenous waste because the build-up of ammonia is ultimately deadly. The term urea cycle disorder (UCD) describes a body’s deficiency in the breakdown of nitrogen-containing proteins and molecules. The severity of the disorder depends on the shortage of the carbamol-phosphate synthase 1, ornithine transcarbamylase, argininosuccinate synthetase, and argininosuccinate lyase enzymes, as well as the absence of the cofactor producer N-acetylglutamate synthase in the urea cycle. Infants with severe UCD typically show signs of ailments shortly after birth ,which can include cerebral edema, lethargy, anorexia, hyperventilation, hypoventilation, hypothermia, seizures, neurologic posturing, and coma. In patients with milder urea cycle disorders and arginase deficiency, ammonia accumulation rapidly develops following illness or stress. Urea cycle disorder increases the plasma ammonia concentration, though symptoms and clinically recognizable episodes are not visible for the first few months or decades of the disorder. The management of UCD manifestations can vary from restricting the protein for two to twenty-four hours to minimizing nitrogen consumption to prescribing intravenous fluids and cardiac pressors.

Molecular and biochemical genetic testing is essential in the diagnosis of UCD. Plasma ammonia concentrations above 150 (mol/L, along with a normal anion gap and plasma glucose concentration, indicate the manifestation of UCD. Given the many varieties of UCD, additional plasma quantitative amino acid analyses and measurements of the urinary orotic acid must be performed to differentiate and distinguish particular disorders. Molecular genetic testing is capable of discerning specific urea cycle defects and, along with enzyme activity measurements, can confirm the specific defect of the patient.

The majority of the urea cycle disorders are hereditary. Genetic counselors aid in the molecular genetic testing and prenatal testing of candidate relatives to distinguish particular UCDs if the pathogenic deviations of the disorder are known. Identifying the candidate relatives to the disorder are essential, especially before manifestation and symptoms begin, to allow correct dietary therapy and other preventive measures for hyperammonemia.

Bibliography

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