Hyperammonaemia in cats

The metabolism of ammonia is complex, yet a vitally important process required to maintain physiological homeostasis. Ammonia production is a by-product of the catabolism of nitrogen sources, most notably ingested protein and amino acids. Since ammonia is neurotoxic at high systemic blood concentrations, efficient mechanisms exist to compartmentalise the production and elimination of ammonia to maintain safe levels. The liver is the major player in ammonia excretion, while the intestine and kidney are the main ammonia producers. The liver can also generate ammonia, and the intestines and kidney can aid in ammonia excretion. Muscle can serve as an ammonia sink and in some cases increase ammonia load, which adds to the complexity of this process.

Ammonia is a biologically important source of nitrogen required for amino acid, protein and nucleic acid synthesis (Walker, 2014; Häberle, 2020; Butterworth, 2021). Additionally, ammonia plays a pivotal role in the kidney's maintenance of acid–base balance. Most ammonia is generated in the gastrointestinal tract from the action of urease-producing microbes on dietary and endogenous proteins (Table 1). The generated ammonia freely diffuses across the intestinal epithelium and makes its way into the portal blood. Additional sources of ammonia production include enterocyte metabolism of glutamine to glutamate in the intestine and kidney which releases ammonia, skeletal muscle production through the purine nucleotide cycle following strenuous exercise and hydrolysis of urea by urease-producing microbes in the gastrointestinal tract (Table 1).