ureases

Ureases are nickel-containing metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. The common overall reaction is (NH2)2CO + H2O → CO2 + 2 NH3. They are widespread in bacteria, plants, and fungi, with notable sources such as jack bean urease (Canavalia ensiformis). Most ureases are multimeric proteins, often forming hexamers with two nickel ions at each active site. The active site features a carbamylated lysine that coordinates two nickel ions, along with several histidine and aspartate residues that facilitate substrate activation and water deprotonation.

Mechanism and function: Substrate urea binds to the dinuclear nickel center. A water-derived hydroxide molecule acts as a nucleophile to attack urea, producing ammonium and carbamate, which rapidly hydrolyzes to ammonium and carbon dioxide. The reaction increases local ammonia concentration and pH, enabling various biological processes. Urease activity plays roles in nitrogen metabolism across plants and microbes. In some pathogens, such as Helicobacter pylori, urease helps survival in acidic environments by neutralizing stomach acid; urease-producing bacteria are also implicated in the formation of struvite kidney stones due to elevated urine pH.

Applications and significance: In microbiology, urease tests identify urease-positive organisms and aid in clinical diagnosis. In agriculture, urease activity drives rapid hydrolysis of urea fertilizers, which can lead to ammonia volatilization; inhibitors such as N-(n-butyl) thiophosphoramide (NBPT) are used to reduce nitrogen losses. Research areas include biotechnology for biomineralization and potential medical interventions targeting urease in pathogens.