Elevated plasma ammonia and glutamine concentrations reflect impairment of concerted nitrogen handling in liver, skeletal muscle, kidneys, and intestine—but what about the brain? As you already know, neurological symptoms are common in patients with hyperammonaemic episodes in general and urea cycle defects in particular. What is happening to ammonia if it enters the brain?
The brain does not have the ability to irreversibly detoxify ammonia using ureagenesis, since urea cycle enzymes are only incompletely expressed in the brain. Excess ammonia can only be transiently stored as glutamine, and citrulline can be recycled to arginine.
Astrocytes are the most important cell type in the brain as far as ammonia metabolism is concerned. They express glutamine synthetase as well as ASS and ASL. These latter two enzymes are increased during hyperammonemia.
