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urea [key], organic compound that is the principal end product of nitrogen metabolism in most mammals. Urea was the first animal metabolite to be isolated in crystalline form; its crystallization was described in the early 18th cent., and in 1773 it was noted that urea gave off ammonia when heated. This discovery provided a clue to its structure. In 1828 urea also became the first organic compound to be synthesized from inorganic materials (lead or silver cyanate and ammonia); this work was done by German chemist Friedrich Wöhler in 1828. Years of investigation of the biosynthesis of urea culminated in the proposal of the ornithine cycle (sometimes known as the Krebs urea cycle, named for German-born chemist Hans Krebs) in 1932. The proposed cycle has since been amended only in detail. It involves the linking of one molecule of ammonia with one molecule of carbon dioxide to form carbamoyl phosphate which then is added to ornithine resulting in the formation of citrulline. Next the nitrogen-containing amino group from aspartic acid is combined with the citrulline, resulting in the formation of arginine. The addition of a water molecule, arginine is then split into one molecule of urea and one molecule of ornithine, which can now repeat the cycle. In metabolism of proteins and other materials, the ammonia molecule that enters the cycle originates from glutamic acid, but glutamic acid can acquire the group that generates this ammonia from many other amino acids; thus most of the nitrogen in protein can eventually be converted to nitrogen in urea. These reactions have been shown to occur in the liver. Urea is transported in the blood to the kidneys, where it is filtered out; its concentration in urine is about 60 to 70 times as great as that in blood.
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