The Vitals: Ammonia-Related Encephalopathy

Ammonia Production:

Ammonia is primarily a by-product of nitrogen metabolism and breakdown of amino acids by bacteria residing in the gut. Along the intestinal wall and primarily in the colon are urease-producing bacteria, among other bacterial species, that can also generate ammonia from the small amount of urea that re-enters the gut via the enterohepatic circulation. Muscle also has the capacity to produce ammonia at a magnitude that correlates with the duration and intensity of muscle work.  In times of intense exercise or during seizures, the higher energy requirements of skeletal muscle drive the generation of ammonia via deamination of adenosine monophosphate in the purine nucleotide cycle along with breakdown of branched-chain amino acids.

Ammonia Degradation:

Despite the constant production of ammonia by the tissues, its concentration in the systemic circulation is kept at a minimum primarily by the hepatocytes of the liver. These cells contain the enzymes that facilitate the urea cycle, a process by which ammonia is detoxified to urea, a much less toxic form. A large portion of the urea formed by the liver is taken up by the kidneys where it plays a vital role in renal handling and excretion of acid. The small portion that remains re-enters the enterohepatic circulation and is hydrolyzed to ammonia by urease-producing bacteria.  Skeletal muscle has the capacity to provide some buffering capacity in situations where serum ammonia levels are high.  It does this through conversion of ammonia to glutamine using the enzyme, glutamine synthetase. This enzyme is also present in the astrocytes of brain tissue and is used to provide a constant source of glutamine used in the synthesis of two important neurotransmitters: glutamate and GABA.