Urease is an enzyme that acts as a biological catalyst to accelerate a specific chemical reaction. It is a metalloenzyme, meaning its structure contains metal ions; specifically, two nickel ions in its active site. One nickel ion helps to bind and position the target molecule, while the second activates a water molecule that participates in the reaction.
Biochemical Function of Urease
The primary role of urease is to catalyze the hydrolysis of urea. In this reaction, urea and water break down into carbon dioxide and two molecules of ammonia. This process increases the rate of urea breakdown.
Without a catalyst, urea is a stable compound with a degradation half-life estimated at 3.6 years under normal conditions. In the presence of urease, this same reaction is accelerated by a factor of approximately 10^14, making it one of the most proficient enzymes known. A consequence of this reaction is the production of ammonia, a weak base. As ammonia accumulates, it causes a substantial increase in the local pH, making the environment more alkaline.
Natural Occurrence of Urease
Urease is found widely throughout the biological world, produced by a diverse range of organisms including bacteria, archaea, fungi, algae, and many plants. Its primary function in these organisms is to provide a usable source of nitrogen for growth by breaking down urea. In the bacterial kingdom, urease is produced by many species, including those with medical and environmental relevance such as Helicobacter pylori, Proteus mirabilis, and Klebsiella aerogenes.
Among fungi, yeasts like Cryptococcus neoformans utilize urease. The enzyme is also abundant in the seeds of certain plants, particularly legumes. The jack bean (Canavalia ensiformis) is a classic source, and its urease was the very first enzyme to be crystallized in 1926, a significant achievement in biochemistry. In plants, urease helps metabolize nitrogen-containing compounds for processes like seed germination.
Role of Urease in Human Health and Disease
Urease activity is a factor in the pathology of several human diseases, particularly those involving the stomach and urinary tract. The bacterium Helicobacter pylori uses urease as a primary mechanism for survival in the highly acidic environment of the human stomach. By producing large quantities of the enzyme, H. pylori hydrolyzes urea present in the stomach to generate a protective cloud of ammonia. This ammonia neutralizes gastric acid, allowing the bacterium to colonize the stomach lining, which can lead to chronic inflammation (gastritis) and peptic ulcers.
This unique function of H. pylori’s urease is exploited for diagnostic purposes. The urea breath test is a non-invasive procedure used to detect an active infection. A patient ingests urea labeled with a specific carbon isotope (carbon-13 or carbon-14). If H. pylori is present, its urease will break down the labeled urea, producing labeled carbon dioxide that travels through the bloodstream to the lungs and is then detected in the patient’s exhaled breath.
In the urinary system, urease-producing bacteria are a primary cause of certain types of urinary tract infections (UTIs) and the formation of infection-induced kidney stones. The bacterium Proteus mirabilis is a common culprit, thriving in the urinary tract and producing urease that breaks down urea in the urine. The resulting ammonia production makes the urine alkaline, causing mineral compounds that are normally soluble to precipitate and crystallize. This process leads to the formation of stones composed of magnesium ammonium phosphate, known as struvite stones, which can grow large and cause kidney damage.
Agricultural and Environmental Impact
Beyond its medical relevance, urease impacts agriculture and the environment through its role in the global nitrogen cycle. Soil microorganisms widely produce urease to break down urea from natural sources, making nitrogen available for plant growth. This process is important due to the widespread use of urea as a nitrogen fertilizer, valued for its high nitrogen content and low cost.
When urea-based fertilizers are applied to soil, the native urease enzymes rapidly hydrolyze the urea into ammonia. This rapid conversion can lead to significant nitrogen loss through a process called ammonia volatilization, where the ammonia escapes into the atmosphere as a gas before plants can absorb it. This reduces the efficiency of the fertilizer, meaning farmers get less value for their investment, and contributes to environmental pollution. Atmospheric ammonia can lead to soil acidification and can disrupt ecosystems when it is redeposited.
To counter this problem, agricultural science has developed urease inhibitors. These chemical compounds, such as N-(n-butyl)thiophosphoric triamide (NBPT), are added to urea fertilizers to temporarily block the activity of soil urease. By slowing the rate of urea hydrolysis, these inhibitors ensure that nitrogen remains in the soil longer, reducing losses from ammonia volatilization and improving its availability for crop uptake. This approach enhances fertilizer efficiency and mitigates the negative environmental effects associated with urea use.