Gosset Molecular Classification
Metabolic Pathway
Other Names
Urea Cycle, Glutamine Synthesis Pathway, Nitrogen Detoxification, Ammonia Metabolism
Disease Roles
Ammonia Detoxification Pathway Overview
The Ammonia detoxification pathway encompasses coordinated enzymatic processes—primarily the hepatic urea cycle supplemented by extrahepatic glutamine synthesis—that convert potentially toxic free ammonia into non-toxic compounds suitable for elimination from the body. Dysfunction at any step may have serious clinical consequences including neurological impairment.
Mechanism of Action
Ammonia scavengers bind to ammonia, forming compounds that are excreted in urine. Lactulose promotes ammonia excretion in feces. Rifaximin reduces ammonia-producing bacteria in the gut. Glycerol phenylbutyrate is converted to phenylacetate, which binds to glutamine and promotes its excretion.
Biological Functions
Ammonia detoxification
Nitrogen balance
Urea production
Glutamine synthesis
Acid-base balance (renal)
Disease Associations
Hepatic encephalopathy
Hyperammonemia
Urea cycle disorders
Liver failure
Renal failure
Safety Considerations
- Hyperammonemia can lead to neurological damage and death
- Rapid correction of hyperammonemia can cause cerebral edema
- Ammonia scavengers can have side effects such as nausea, vomiting, and electrolyte imbalances
- Lactulose can cause diarrhea and abdominal cramping
Interacting Drugs
Ammonia scavengers (e.g., sodium benzoate, sodium phenylacetate)
Lactulose
Rifaximin
Glycerol phenylbutyrate
Associated Biomarkers
| Biomarker |
|---|
| Plasma ammonia levels |
| Plasma glutamine levels |
| Urine urea levels |
| Arterial blood pH |
| Liver function tests (AST, ALT, bilirubin) |