Urease

Ureases (EC 3.5.1.5), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-containing metalloenzymes of high molecular weight. Ureases (EC 3.5.1.5), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-containing metalloenzymes of high molecular weight. These enzymes catalyze the hydrolysis of urea into carbon dioxide and ammonia: The hydrolysis of urea occurs in two stages. In the first stage, ammonia and carbamate are produced. The carbamate spontaneously and rapidly hydrolyzes to ammonia and carbonic acid. Urease activity increase the pH of its environment as it produces ammonia, which is basic. Urease is also found in mammals and humans, the presence of urease is considered to be very harmful to mammals due to the production of the toxic ammonia product. However, mammalian cells do not produce urease, in fact, the sources are the various bacteria in the body, specifically in the intestine. European hare (Lepus europaeus), a class of Mammalia, was discovered to have high urease activity in its large intestine, a part of gastrointestinal tract. Previously, other mammals i.e. rats, pigs and rabbits, with postgastric fermentation were detected with lower urease activity compared to European Hare. In human kidneys, urea is present in order for everyday functions and is estimated that per day, a healthy adult excretes about 10 to 30 g of urea. Other than urea being found in urine, it is also present in sweat, blood serum and stomach. Inside the mitochondria of a liver cell, excess ammonia is converted to urea through the urea cycle and if some excess ammonia is still present in the mitochondria, then it gets used up for protein synthesis. There are specific tissues involved during urea processing which are epithelial, extrahepatic and muscle tissues. With the production of ammonia and amino acids, the cell proteins are broken down by proteolytic enzymes already present in the muscle tissue. Similarly, identical cell proteins are predicted to convert previously broken down ammonia into urea. Once the urea is formed in the liver, it is excreted through urine after passing from bloodstream and the kidneys. Its activity was first identified in 1876 by Frédéric Alphonse Musculus as a soluble ferment. In 1926, James B. Sumner, showed that urease is a protein by examining its crystallized form. Sumner's work was the first demonstration that a protein can function as an enzyme and led eventually to the recognition that most enzymes are in fact proteins. Urease was the first enzyme crystallized. For this work, Sumner was awarded the Nobel prize in chemistry in 1946. The crystal structure of urease was first solved by P. A. Karplus in 1995. A 1984 study focusing on urease from jack bean found that the active site contains a pair of nickel centers. In vitro activation also has been achieved with manganese and cobalt in place of nickel. Lead salts are inhibiting. The molecular weight is either 480 kDa or 545 kDa for jack-bean urease (calculated mass from the amino acid sequence). 840 amino acids per molecule, of which 90 are cysteine residues. The optimum pH is 7.4 and optimum temperature is 60 °C. Substrates include urea and hydroxyurea. Bacterial ureases are composed of three distinct subunits, one large (α 60–76kDa) and two small (β 8–21 kDa, γ 6–14 kDa) commonly forming (αβγ)3 trimers stoichiometry with a 2-fold symmetric structure (note that the image above gives the structure of the asymmetric unit, one-third of the true biological assembly), they are cysteine-rich enzymes, resulting in the enzyme molar masses between 190 and 300kDa.