Urease is a metalloenzyme that functions as a biological catalyst, accelerating a specific chemical reaction in various organisms. Its catalytic activity depends on two nickel ions housed at its active site. Urease’s sole function is to break down urea, a nitrogen-containing waste product, making the nitrogen available for use by the organism.
How Urease Breaks Down Urea
The core function of urease is the hydrolysis of urea (\(text{(NH}_2)_2text{CO}\)), which involves breaking its chemical bonds using water. Urea is broken down into two simpler molecules: carbon dioxide (\(text{CO}_2\)) and ammonia (\(text{NH}_3\)). Urease highly accelerates this natural process, increasing the reaction rate by a factor of up to one-hundred-trillion.
The hydrolysis occurs in two main steps. First, urea is converted into ammonia and an unstable compound called carbamic acid. The carbamic acid then spontaneously breaks down, yielding a second molecule of ammonia and carbonic acid. The production of two ammonia molecules is biologically significant because ammonia is a weak base. This release drastically increases the alkalinity, or pH, of the surrounding environment. The nickel ions in the enzyme’s active site facilitate this chemical breakdown by binding to the urea molecule.
The Natural Sources of Urease
Urease is widespread in nature, found in many plants, fungi, and bacteria, where it plays a significant role in the global nitrogen cycle. Its presence allows these organisms to utilize urea as a nitrogen source for growth and metabolism. In the plant kingdom, leguminous seeds are particularly rich sources of the enzyme, such as urease from the jack bean (Canavalia ensiformis).
Fungal species, including Aspergillus and Penicillium, also produce urease to acquire nitrogen from urea. The enzyme is most often associated with bacteria, particularly those in the soil, which use urease to convert urea-based fertilizers into usable nitrogen compounds. While many bacterial species are urease-positive, the enzyme is not generally produced by animal cells. Therefore, its presence in mammalian tissues often indicates microbial activity.
Urease in Medical Diagnosis and Disease
The urease enzyme is responsible for the survival and pathogenicity of the bacterium Helicobacter pylori (H. pylori), a common cause of chronic gastritis and peptic ulcers in humans. The acidic environment of the human stomach, with a \(text{pH}\) often below 4, is generally inhospitable to bacteria, but H. pylori uses urease as a defense mechanism.
The bacterium hydrolyzes urea present in the stomach lining into ammonia, which acts as a powerful buffer. This localized ammonia production neutralizes the surrounding stomach acid, creating a protective microenvironment that allows H. pylori to colonize the gastric mucosa.
The activity of this bacterial enzyme forms the basis for the Urea Breath Test (UBT), a common non-invasive diagnostic tool for H. pylori infection. In the UBT, a patient ingests tagged urea. If H. pylori is present, its urease breaks the urea down, releasing labeled carbon dioxide that is detected in the patient’s exhaled breath.
Urease activity is also implicated in the formation of struvite kidney stones. Bacteria that cause urinary tract infections, such as Proteus mirabilis, produce urease, which breaks down urea in the urine. This reaction dramatically raises the urine \(text{pH}\), creating an alkaline environment. This environment promotes the crystallization of magnesium ammonium phosphate, leading to the formation of these infection-induced stones.