From the FDA Drug Label
Two moles of nitrogen are removed per mole of phenylacetate when it is conjugated with glutamine. The nitrogen content of phenylacetylglutamine per mole is identical to that of urea (both contain two moles of nitrogen) The second nitrogen in urea comes from ammonia via the urea cycle, but in the context of sodium phenylacetate, it comes from glutamine when phenylacetate is conjugated with it to form phenylacetylglutamine 1.
From the Research
The second nitrogen in urea comes from ammonia (NH3). Urea, with the chemical formula CO(NH2)2, contains two nitrogen atoms. During the urea cycle in the liver, the first nitrogen is derived from ammonia that enters the cycle as carbamoyl phosphate, while the second nitrogen comes directly from free ammonia that combines with citrulline to form arginine, which is then cleaved to produce urea 2. This process is crucial for eliminating excess nitrogen from the body, particularly from protein metabolism. The urea cycle effectively converts toxic ammonia into urea, a water-soluble compound that can be safely excreted in urine.
The urea cycle is the primary nitrogen-disposal pathway in humans, requiring the coordinated function of six enzymes and two mitochondrial transporters to catalyze the conversion of a molecule of ammonia, the α-nitrogen of aspartate, and bicarbonate into urea 2. Accumulation of ammonia and other toxic intermediates of the cycle lead to predominantly neurologic sequelae. The disorders may present at any age from the neonatal period to adulthood, with the more severely affected patients presenting earlier in life.
Key points to consider:
- The urea cycle is essential for nitrogen homeostasis in the body, preventing ammonia toxicity which could otherwise lead to neurological damage 2.
- The second nitrogen in urea comes from free ammonia that combines with citrulline to form arginine, which is then cleaved to produce urea 2.
- Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea 3.
- The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known 4.
In terms of morbidity, mortality, and quality of life, it is crucial to understand the urea cycle and its role in eliminating excess nitrogen from the body. This knowledge can help guide the management of urea cycle disorders and prevent ammonia toxicity, which can have severe neurological consequences 2.